| 1. |
- Abdalla, Hana, et al.
(författare)
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Effects of CNI-1493 on human granulocyte functions
- 2006
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 211:3, s. 191-197
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Tidskriftsartikel (refereegranskat)abstract
- During acute bacterial infections such as sepsis and meningitis, activation of inflammatory mediators such as nitric oxide (NO) plays a crucial role in both pathogenesis and host defense. We have previously reported that CNI-1493, a macrophage deactivator, reduced mortality in infant rats infected with Haemophilus influenzae type b (Hib) with associated decrease in the number of granulocytes in the infected tissue. The aim of the present study was to investigate how CNI-1493 affects granulocytes and macrophages in vitro. Murine macrophages (RAW 264.7) pre-incubated with CNI-1493 prior to activation with lipopolysaccharide (LPS)/interferon gamma (IFNγ) had decreased NO production measured as NO2−/NO3− levels and reduction in inducible NO-synthase (iNOS) expression. Reactive oxygen species (ROS) production was increased in formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated granulocytes following CNI-1493 treatment, whereas F-actin content, motility and chemotaxis were decreased under the same conditions. The effects of CNI-1493 on both NO production in LPS/IFNγ-activated macrophages and ROS production, F-actin content, motility and chemotaxis in granulocytes, may contribute to the reduced inflammatory response and increased survival in Hib-infected animals treated with CNI-1493.
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| 2. |
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| 3. |
- Barbosa-Lorenzi, Valéria C, et al.
(författare)
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Curdlan induces selective mast cell degranulation without concomitant release of LTC4, IL-6 or CCL2
- 2017
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 222:4, s. 647-650
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells are sentinel cells with a tissue-specific localization in the interface between the host and the external environment. Their quick and selective response upon encountering pathogens is part of the innate host response and typically initiates the following adaptive immune response. Among several pattern recognition receptors (PRRs) involved in the recognition of pathogens by mast cells, the C-type lectin receptor Dectin-1 has been associated with the recognition of fungi. Our previous studies have shown that mast cells are the predominant cell type expressing Dectin-1 in human skin, and they also recognize and respond to Malassezia sympodialis by producing cytokines connected to the innate host response and upregulating the expression of Dectin-1. In the present study, we investigated mast cell responses to Curdlan, a β-glucan that acts as an agonist for the fungi receptor Dectin-1, and found a unique response pattern with induced degranulation, but surprisingly without synthesis of Leukotriene C4, IL-6 or CCL2. Since mast cells are the predominant Dectin-1 expressing cell in the human skin, this study suggests that mast cell degranulation in response to fungi is an important part of the first line of defense against these pathogens.
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| 4. |
- Bratland, Eirik, et al.
(författare)
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Autoantibodies against aromatic amino acid hydroxylases in patients with autoimmune polyendocrine syndrome type 1 target multiple antigenic determinants and reveal regulatory regions crucial for enzymatic activity
- 2013
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 218:6, s. 899-909
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Tidskriftsartikel (refereegranskat)abstract
- Patients with autoimmune polyendocrine syndrome type 1 (APS-1) frequently have autoantibodies directed against the aromatic amino acid hydroxylases tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH). We aimed to characterize these autoantibodies with regard to their antigenic determinants, their influence on enzymatic activity and their clinical associations. In particular, we wanted to compare autoantibodies against the two different isoforms of TPH, which display different tissue distribution. Using sera from 48 Scandinavian APS-1 patients we identified 36 patients (75%) with antibodies against one or more of these three enzymes. Antibodies against TPH1, but not TPH2, were associated with malabsorption in the whole Scandinavian cohort, while TH antibodies were associated with dental enamel hypoplasia in Norwegian patients. Subsequent experiments with selected patient sera indicated that while the C-terminal domain was the immunodominant part of TPH1, the epitopes of TPH2 and TH were mainly located in the N-terminal regulatory domains. We also identified a TPH1 specific epitope involved in antibody mediated inhibition of enzyme activity, a finding that provides new insight into the enzymatic mechanisms of the aromatic amino acid hydroxylases and knowledge about structural determinants of enzyme autoantigens. In conclusion, TPH1,TPH2 and TH all have unique antigenic properties in spite of their structural similarity.
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| 5. |
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| 6. |
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| 7. |
- Cholujová, Dana, et al.
(författare)
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Comparative study of four fluorescent probes for evaluation of natural killer cell cytotoxicity assays
- 2008
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Ingår i: Immunobiology. - : Elsevier. - 0171-2985 .- 1878-3279. ; 213:8, s. 629-640
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Tidskriftsartikel (refereegranskat)abstract
- Cytotoxicity is one of the major defence mechanisms against both virus-infected and tumor cells. Radioactive 51chromium (51Cr) release assay is a “gold standard” for assessment of natural killer (NK) cytolytic activity in vitro. Several disadvantages of this assay led us to design alternative tools based on flow cytometry analysis. Four different fluorescent dyes, calcein acetoxymethyl ester (CAM), carboxyfluorescein succinimidyl ester (CFSE), Vybrant DiO (DiO) and MitoTracker Green (MTG) were tested for labeling of NK target K-562 cells. Target staining stability, spontaneous release of fluorochromes and subsequent accumulation in bystander unstained cells were measured using fluorimetry and flow cytometry. Healthy donor peripheral blood mononuclear cells and affinity column purified NK cells were used as effectors coincubated with target K-562 cells at different E:T ratios for 3h and 90min, respectively. Fluorescent probe 7-amino-actinomycin D was used for live and dead cell discrimination. Bland–Altman statistical method was applied to measure true agreement for all CAM–51Cr, CFSE–51Cr, DiO–51Cr and MTG–51Cr pairs analyzed. Based on the data, none of the four proposed methods can be stated equivalent to the standard 51Cr release assay. Considering linear relationships between data obtained with four fluorochromes and 51Cr release assay as well as linear regression analysis with R2=0.9393 value for CAM–51Cr pair, we found the CAM assay to be the most closely related to the 51Cr assay.
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| 8. |
- Ding, Zhoujie, et al.
(författare)
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IgM-mediated enhancement of immune responses
- 2012
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 217:11, s. 1177-1178
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Djedovic, Neda, et al.
(författare)
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Comparison of dendritic cells obtained from autoimmunty-prone and resistant rats
- 2019
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Ingår i: Immunobiology. - : ELSEVIER GMBH. - 0171-2985 .- 1878-3279. ; 224:3, s. 470-476
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DC) are responsible for the initiation and shaping of the adaptive immune response and are in the focus of autoimmunity research. We were interested in comparison of DC obtained from autoimmunity-prone Dark Agouti (DA) rats and autoimmunity-resistant Albino Oxford (AO) rats. DC were generated from bone marrow precursors and matured (mDC) by lipopolysaccharide. Tolerogenic DC (tolDC) obtained by vitamin D3 treatment were studied in parallel. Profile of cytokine production was different in AO and DA mDC and tolDC. Expression of MHC class II molecules and CD86 were higher in DA DC, while vitamin D3 reduced their expression in dendritic cells of both strains. Allogeneic proliferation of CD4(+) T cells was reduced by AO tolDC, but not with DA tolDC in comparison to respective mDC. Finally, expression of various genes identified as differentially expressed in human mDC and tolDC was also analyzed in AO and DA DC. Again, AO and DA DC differed in the expression of the analyzed genes. To conclude, AO and DA DC differ in production of cytokines, expression of antigen presentation-related molecules and in regulation of CD4(+) T proliferation. The difference is valuable for understanding the divergence of the strains in their susceptibility to autoimmunity.
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| 10. |
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| 11. |
- Ferreira, David Wilson, et al.
(författare)
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CD163 overexpression using a macrophage-directed gene therapy approach improves wound healing in ex vivo and in vivo human skin models
- 2020
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 225:1
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Tidskriftsartikel (refereegranskat)abstract
- Large tissue damage or wounds cause serious comorbidities and represent a major burden for patients, families, and health systems. Due to the pivotal role of immune cells in the proper resolution of inflammation and tissue repair, we focus our current study on the interaction of macrophages with skin cells, and specifically on the effects of CD163 gene induction in macrophages in wound healing. We hypothesize that the over-expression of the scavenger receptor gene CD163 in human macrophages would result in a more efficient wound healing process. Using 3D human wounded skin organotypic tissues, we observed that CD163 overexpression in THP-1 and human primary macrophages induced a more efficient re-epithelization when compared to control cells. Using human primary skin cells and an in vitro scratch assay we observed that CD163 overexpression in THP-1 macrophages promoted a more rapid and efficient wound healing process through a unique interaction with fibroblasts. The addition of CD163-blocking antibody, but not isotype control, blocked the efficient wound healing process induced by CD163 overexpression in macrophages. We found that the co-culture of skin cells and CD163 overexpressing macrophages reduced monocyte chemoattractant protein (MCP)-1 and enhanced tumor growth factor (TGF)-alpha, without altering interleukin (IL)-6 or TGF-beta. Our findings show that CD163 induces a more efficient wound healing and seems to promote a wound milieu with a pro-resolution molecular profile. Our studies set the foundation to study this approach in in vivo clinically relevant settings to test its effects in wound healing processes such as acute major injuries, large surgeries, or chronic ulcers.
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| 12. |
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| 13. |
- Giusti, Pablo, 1975-, et al.
(författare)
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The novel anti-rheumatic compound Rabeximod impairs differentiation and function of human pro-inflammatory dendritic cells and macrophages
- 2011
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 216:1-2, s. 243-250
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Tidskriftsartikel (refereegranskat)abstract
- Rabeximod (9-chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indolo[2,3-b]quinoxaline) is a synthetic compound that is currently being developed for the treatment of rheumatoid arthritis (RA). Here, we investigated the effects of Rabeximod on the functionality of human antigen-presenting cells (APCs) of myeloid origin. Different subsets of professional APCs were generated from human monocytes in vitro and simultaneously treated with different doses of Rabeximod. Although Rabeximod had no effect on the differentiation of monocytes into anti-inflammatory macrophages (AI-Ms), this compound impaired monocyte differentiation into monocyte-derived dendritic cells (MDCs) and pro-inflammatory allostimulated macrophages (Allo-Ms). MDCs that were treated with Rabeximod resulted in a significant decrease in their ability to pinocytose antigens, while no effect was exerted by the drug on the ability of Allo-Ms and AI-Ms to phagocytose. Furthermore, we observed a significant reduction in the allostimulatory ability of MDCs and Allo-Ms after treatment with Rabeximod, although this compound did not affect the low immunostimulatory capacity of AI-Ms. Conversely, the effect of Rabeximod in influencing cytokine secretion by APCs appeared to be limited. In conclusion, Rabeximod impairs differentiation of monocytes into different pro-inflammatory APCs, leading to impaired immunostimulatory abilities of these cells. Our observations shed light on the cellular mode of action and the immunomodulatory effect of Rabeximod.
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| 14. |
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| 15. |
- Hamad, Osama A., 1978-, et al.
(författare)
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Non-proteolytically activated C3 promotes binding of activated platelets and platelet-derived microparticles to leukocytes via CD11b/CD18
- 2012
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 217:11, s. 1191-1191
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Tidskriftsartikel (refereegranskat)abstract
- Background:We have previously demonstrated that complement component C3 binds to the surface of activated platelets, independent of proteolytic activation. The resulting form of C3, termed C3(H2O), was shown to be a ligand for recombinant CD35 (complement receptor 1, CR1). Previous studies by others have indicated that platelet-leukocyte complex (PLC) formation is dependent on the interaction between platelet exposed P-selectin (CD62P) and its ligand, PSGL-1, on leukocytes. In addition, CD11b/CD18 (Mac-1 or CR3) has been shown to participate in this reaction, but its ligand has not yet been identified.Objective:To test the hypothesis that C3 bound to activated platelets and platelet-derived microparticles (PMPs) can act as a ligand for CD11b/CD18 (CR3) and contribute to PLC formation.Methods and results:Blood cells were depleted of plasma proteins. After extensive washing, C3 was added, and the leukocytes were activated with C5a and the platelets with thrombin receptor-activating peptide (TRAP). PLC formation was detected by flow cytometry (monocytes: CD14+/CD42a+, granulocytes: CD16+/CD42a+). For both granulocytes and monocytes, the addition of C3 significantly enhanced PLC formation. Formation of PLC was inhibited by both anti-P-selectin and anti-CD11b monoclonal antibodies. In addition, PMPs isolated from serum, were found to expose C3(H2O) and bind to leukocytes in a fashion similar to activated platelets.Conclusion:We have identified proteolytically non-activated C3 as a ligand for CD11b in the formation of PLC and possibly the binding of PMPs to leukocytes. This observation most likely has pathophysiological implications for the recently reported links between thrombotic disease and the complement system.
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| 16. |
- Happonen, Kaisa, et al.
(författare)
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Interactions of the complement system with molecules of extracellular matrix: Relevance for joint diseases.
- 2012
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Ingår i: Immunobiology. - : Elsevier BV. - 1878-3279 .- 0171-2985. ; 217:11, s. 1088-1096
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is a highly disabling disease affecting all structures of the joint. Understanding the pathology behind the development of RA is essential for developing targeted therapeutic strategies as well as for developing novel markers to predict disease onset. Several molecules normally hidden within the cartilage tissue are exposed to complement components in the synovial fluid upon cartilage breakdown. Some of these have been shown to activate complement and toll-like receptors, which may enhance an already existing inflammatory response, thereby worsening the course of disease. Other cartilage-resident molecules have in contrast shown to possess complement-inhibitory properties. Knowledge about mechanisms behind pathological complement activation in the joints will hopefully lead to methods which allow us to distinguish patients with pathological complement activation from those where other inflammatory pathways are predominant. This will help to elucidate which patients will benefit from complement inhibitory therapies, which are thought to aid a specific subset of patients or patients at a certain stage of disease. Future challenges are to target the complement inhibition specifically to the joints to minimize systemic complement blockade.
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| 17. |
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| 18. |
- Hollander, Peter, et al.
(författare)
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Precursor cells and implications of a T-cell inflamed immune response in the pre-malignant setting in Hodgkin lymphoma
- 2020
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 225:1
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Tidskriftsartikel (refereegranskat)abstract
- The etiology of classical Hodgkin lymphoma (cHL) is largely unknown. High serum CD30-levels are associated with increased risk of cHL. Epstein-Barr virus (EBV) is detectable in the tumor cells in 1/3 of cHL cases in the Western world. The PD-1 pathway (T-cell inflamed immune response) might contribute to the pathogenesis by enabling pre-malignant CD30+ or EBV + cells to evade immune surveillance. We aimed to investigate if high infiltrations of CD30+, PD-1+, PD-L1+ and EBV + cells in benign lymph nodes from patients that later develop cHL (cases) (n = 15) were associated with risk of cHL compared to controls (n = 45) with benign lymph nodes from patients that did not develop cHL. Pathology registries including 3500 cH L patients were screened. Lymph nodes were stained with immunohistochemistry and in situ hybridization and the risk for cHL calculated with logistic regression. High CD30-expression by B- and T-cells was associated with a decreased risk of cHL [(OR = 0.10, 95 % CI:0.03-0.39) and (OR = 0.13, 95 % CI:0.01-0.71), respectively], which remained significant for CD30 + B-cells (OR = 0.15, 95 % CI:0.03-0.60) in multivariate analyses. Amount of PD-1+, PD-L1+ and EBV + cells were not statistically significantly associated with risk of cHL. However, the amount of PD-L1+ leukocytes tended to be higher in cases later developing cHL (OR = 2.84, 95 % CI:0.61-12.61). High proportions of potential precursors to cHL, i.e. CD30 + B-cells in benign lymph nodes are not associated with an increased risk of cHL, while a tendency for a T-cell inflamed immune response, i.e. abundant PD-L1+ cells, was observed in biopsies taken prior to the cHL diagnosis.
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| 19. |
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| 20. |
- Håkansson, Gisela, et al.
(författare)
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Epithelial G protein-coupled receptor kinases regulate the initial inflammatory response during mycobacterial infection.
- 2013
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Ingår i: Immunobiology. - : Elsevier BV. - 1878-3279 .- 0171-2985. ; 218:7, s. 984-994
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between mycobacteria and epithelium is unexplored, but may determine the outcome of the infection. We have analyzed the role of two G protein-coupled receptors, CXCR1 and CXCR2 that are important regulators of many pulmonary diseases. We found that mycobacteria significantly increased the expression of both CXCR1 and CXCR2 on alveolar epithelial cells and both receptors were found to be important for neutrophil diapedesis across primary endothelial cells towards infected mucosa. Mycobacteria, lipoarabinomannan or 19-kDa glycolipoprotein up-regulated the inhibitory G protein-coupled receptor kinase (GRK)2, while GRK3 was less affected. Mycobacteria-induced GRK2 up-regulation decreased chemokine transcription and secretion thereby affecting the neutrophil recruitment to infected mucosa. These events were completely abolished by blocking these receptors prior to infection as the blocking increased epithelial immune responses. We have identified novel interactions occurring in the initial phase of mycobacterial infections by which mycobacterial manipulate epithelial inflammatory responses.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Kolbus, Daniel, et al.
(författare)
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Immunization with cationized BSA inhibits progression of disease in ApoBec-1/LDL receptor deficient mice with manifest atherosclerosis.
- 2011
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Ingår i: Immunobiology. - : Elsevier BV. - 1878-3279 .- 0171-2985. ; 216, s. 663-669
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Tidskriftsartikel (refereegranskat)abstract
- Immune responses against modified self-antigens generated by hypercholesterolemia play an important role in atherosclerosis identifying the immune system as a possible novel target for prevention and treatment of cardiovascular disease. It has recently been shown that these immune responses can be modulated by subcutaneous injection of adjuvant. In the present study we immunized 25-week old ApoBec-1/LDL receptor deficient mice with manifest atherosclerosis with adjuvant and two different concentrations of the carrier molecule cationized BSA (cBSA). Plasma levels of Th2-induced apolipoprotein B (apoB)/IgG1 immune complexes were increased in the cBSA immunized groups verifying induction of immunity against a self-antigen. Mice were sacrificed at 36 weeks of age and atherosclerosis was monitored by en face Oil red O staining of the aorta. Immunization with 100μg cBSA inhibited plaque progression, whereas the lower dose (50μg) did not. In addition, the higher dose induced a more stable plaque phenotype, indicated by a higher content of collagen and less macrophages and T cells in the plaques. Moreover, there was an increased ratio of Foxp3(+)/Foxp3(-) T cells in the circulation suggesting activation of a regulatory T cell response. In conclusion, we show that immunization with cBSA induces an immune response against apoB as well as an activation of Treg cells. This was associated with development of a more stable plaque phenotype and reduced atherosclerosis progression.
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Lagunas-Rangel, Francisco Alejandro, et al.
(författare)
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What do we know about the antibody responses to SARS-CoV-2?
- 2021
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 226:2
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Forskningsöversikt (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a pandemic with millions of infected people and deaths. Currently, the scientific community is working hard to develop a specific vaccine or treatment. However, since antibody production is an important part of the adaptive immune response, to develop vaccines and therapies, we must understand the antibody response to SARS-CoV-2 infection. In this work, we summarize the most important findings of antibody-mediated immunity against SARS-CoV-2 and highlight its role in the efficient use of plasma from convalescent patients and the direct application of antibodies as treatment.
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| 29. |
- Lindelöf, Linnea, et al.
(författare)
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62 Acquired ficolin-3 deficiency in patients with Systemic Lupus Erythematosus
- 2023
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Ingår i: Immunobiology. - : Elsevier. - 0171-2985 .- 1878-3279. ; 228:5, s. 152515-152515
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ficolin-3 is the main initiator of the lectin pathway in humans. Case reports of ficolin-3 deficient patients have suggested that ficolin-3 deficiency may be enriched in patients with Systemic Lupus Erythematosus (SLE), a systemic autoimmune disease where complement plays an important role. Therefore, this study aimed to investigate the activity levels of ficolin-3 and to identify potential ficolin-3 deficient individuals in two Swedish SLE cohorts.Methods: Serum or plasma samples from SLE patients (n=810) and matched controls (n=566) were collected from the Karolinska Institute (KI) and Umeå University Hospital. The ficolin-3 activity levels were measured by an in-house developed functional ELISA with a pooled normal human serum sample as a reference. Serial samples were analyzed for ficolin-3 deficient patients when available. Sequencing data were analyzed for FCN3 frame-shift mutation +1637delC (rs532781899) and other potential loss-of-function (LoF) variants.Results: This screening revealed that the level of ficolin-3 activity varies largely in patients with SLE. The activity levels also show that SLE patients seem to generally have elevated ficolin-3 activity compared to the control group (p<0.0001). Out of 810 patients with SLE, four patients were determined to be ficolin-3 deficient. For two of these patients, the ficolin-3 activity was at normal levels at the time of diagnosis and thereafter depleted over time, indicating an acquired deficiency. For deficient patients, no or very low ficolin-3 protein levels and no lectin pathway-dependent complement activation could be detected. Autoantibodies against ficolin-3 were not detectable. No patients were homozygous for the +1637delC frameshift mutation, whereas in total 10 patients were determined to be heterozygous carriers. These heterozygous patients displayed lower levels of ficolin-3 activity but did not include the deficient patients. Additional possible LoF variants were analyzed but none were enriched in either patients or controls.Conclusions: Contrary to the classical pathway of the complement system we show that genetic ficolin-3 deficiency is not a risk factor for SLE. Instead, acquired ficolin-3 deficiency was observed in a subgroup of SLE patients, possibly due to a potent activation of the lectin pathway that depleted ficolin-3 plasma levels in these individuals.
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| 30. |
- López-González, Moisés, et al.
(författare)
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Human keratinocyte cultures (HaCaT) can be infected by DENV, triggering innate immune responses that include IFN lambda and LL37
- 2018
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 223:11, s. 608-617
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Tidskriftsartikel (refereegranskat)abstract
- The skin is the first anatomical region that dengue virus (DENV) encounters during the natural infection. Although the role of some skin resident cells like dendritic cells and fibroblasts has been demonstrated to be crucial to elucidate the role of resident cells and molecules participating during the early events of the innate immune response, the participation of keratinocytes during DENV infection has not been fully elucidated. In this paper we aimed to evaluate the use of the HaCaT cell line as a model to study the immune responses of skin keratinocytes to DENV infection. We demonstrated productive DENV-2 infection of HaCaT cells and their capability to establish an antiviral response through production of type I and type III interferons (IFN-beta and IFN-lambda). The production of these cytokines by HaCaT cells correlated with upregulation of IFN-inducible transmembrane protein-3 (IFITM3) and viperin in bystander, uninfected cells. We also observed an increase in secretion of IL-6 and IL-8. Skin keratinocytes are known to secrete antimicrobial peptides (AMPs) during viral infections. In our model, DENV-2 infected HaCaT cells upregulate the production of cytoplasmic LL-37. We evaluated the dual role of LL-37, HBD2, and HBD3 antiviral activity and immunoregulation during DENV-2 infection of HaCaT cells and found that LL-37 significantly reduced DENV-2 replication. This indicates that the HaCaT cell line can be used as a model for studying the innate response of keratinocytes to DENV infection. Our results also suggest that skin keratinocytes play an important role in the skin microenvironment after DENV infection by secreting molecules like type I and type III IFNs, pro-inflammatory molecules, and LL-37, which may contribute to the protection against arboviral infections.
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| 31. |
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| 32. |
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| 33. |
- Mårtensson, Ulla, et al.
(författare)
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Anders G. Sjoholm - Obituary
- 2007
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Ingår i: Immunobiology. - : Elsevier BV. - 1878-3279 .- 0171-2985. ; 212:4-5, s. 427-427
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 34. |
- Nilsson, Bo, et al.
(författare)
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The tick-over theory revisited : Is C3 a contact-activated protein?
- 2012
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 217:11, s. 1106-1110
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Forskningsöversikt (refereegranskat)abstract
- The tick-over theory was first introduced in the 1970s to explain the presence of the initial C3b molecules, which are able to trigger complement activation by the alternative pathway in human plasma under physiological conditions. After the identification of the thioester, the predominant hypothesis has been that this bond is hydrolyzed at a slow but constant rate by nucleophilic attack by H2O, leading to the generation of C3(H2O). Here we put forward the hypothesis that the rate of hydrolysis of C3 to C3(H2O) may be greatly accelerated by the interaction between C3 and a number of biological and artificial interfaces, including gas bubbles, biomaterial surfaces and different lipid surfaces and complexes. We therefore propose that C3 should preferentially be regarded as a contact activated protein rather than a target for passive, random hydrolysis in the fluid phase. (C) 2012 Elsevier GmbH. All rights reserved.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Persson, Emma, et al.
(författare)
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The diverse ontogeny and function of murine small intestinal dendritic cell/macrophage subsets.
- 2010
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Ingår i: Immunobiology. - : Elsevier BV. - 1878-3279 .- 0171-2985. ; Jul 1, s. 692-697
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal dendritic cell and macrophage subsets are believed to play key roles in maintaining intestinal homeostasis in the steady state and in driving protective immune responses in the setting of intestinal infection. This mini-review focuses on recent progress regarding the ontogeny and function of small intestinal lamina propria dendritic cell/macrophage subsets. In particular we discuss recent findings suggesting that small intestinal CD103(+) dendritic cells and Cx3cr1(+) cells derive from distinct precursor populations and that CD103(+) dendritic cells represent the major migratory population of cells with a key role in initiating adaptive immune responses in the draining mesenteric lymph node. In contrast, Cx3cr1(+) cells appear to represent a tissue resident population, phenotypically indistinguishable from tissue resident macrophages. These latter observations suggest an important division of labour between dendritic cell/macrophage subsets in the regulation of intestinal immune responses in the steady state.
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| 39. |
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| 40. |
- Prohaszka, Zoltan, et al.
(författare)
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Complement analysis 2016 : Clinical indications, laboratory diagnostics and quality control
- 2016
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 211:11, s. 1247-1258
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, complement analysis of body fluids and biopsies, going far beyond C3 and C4, has significantly enhanced our understanding of the disease process. Such expanded complement analysis allows for a more precise differential diagnosis and for critical monitoring of complement-targeted therapy. These changes are a result of the growing understanding of the involvement of complement in a diverse set of disorders. To appreciate the importance of proper complement analysis, it is important to understand the role it plays in disease. Historically, it was the absence of complement as manifested in severe infection that was noted. Since then complement has been connected to a variety of inflammatory disorders, such as autoimmune diseases and hereditary angioedema. While the role of complement in the rejection of renal grafts has been known longer, the significant impact of complement. In certain nephropathies has now led to the reclassification of some rare kidney diseases and an increased role for complement analysis in diagnosis. Even more unexpected is that complement has also been implicated in neural, ophtalmological and dermatological disorders. With this level of involvement in some varied and impactful health issues proper complement testing is clearly important; however, analysis of the complement system varies widely among laboratories. Except for a few proteins, such as C3 and C4, there are neither well-characterized standard preparations nor calibrated assays available. This is especially true for the inter-laboratory variation of tests which assess classical, alternative, or lectin pathway function. In addition, there is a need for the standardization of the measurement of complement activation products that are so critical in determining whether clinically relevant complement activation has occurred in vivo. Finally, autoantibodies to complement proteins (e.g. anti-C1q), C3 and C4 convertases (C3 and C4 nephritic factor) or to regulatory proteins (e.g. anti-Clinhibitor, anti-factor H) are important in defining autoimmune processes and diseases based on complement dysregulation. To improve the quality of complement laboratory analysis a standardization commmittee of the International Complement Society (ICS) and the International Union of Immunological Societies (IUIS) was formed to provide guidelines for modern complement analysis and standards for the development of international testing programs.
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| 44. |
- Skoglund, Caroline, et al.
(författare)
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C1q induces a rapid up-regulation of P-selectin and modulates collagen- and collagen-related peptide-triggered activation in human platelets
- 2010
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Ingår i: Immunobiology. - Jena, Germany : Elsevier. - 0171-2985 .- 1878-3279. ; 215:12, s. 987-995
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Tidskriftsartikel (refereegranskat)abstract
- Blood platelets are emerging as important immunomodulatory cells, but complement interaction with platelets is not well understood. Several platelet structures have been described as complement protein 1q (C1q) binding receptors, such as C1qRp/CD93 and gC1qR. However, there are conflicting results whether these receptors are C1q binding structures, or even at all expressed on the cell surface. Recently, the collagen-binding integrin alpha II beta I was reported to bind C1q on mast cells, and this receptor is also present on platelets. The aim of this study was to further characterize the effects of C1q on platelets, by quantifying the platelet surface expression of P-selectin (CD62P) and monitoring the formation of platelet-neutrophil aggregates. Using flow cytometry, we found that C1q dose-dependently triggered a rapid but moderate and transient up-regulation of P-selectin already within 5s of C1q exposure. Pre-incubation with an antibody directed against gC1qR significantly inhibited (with 57% compared to control) the up-regulation, whereas an antibody towards the alpha II beta I-integrin showed no effect. Stimulation with C1q did not change the cytosolic calcium-levels, as measured with the fluorescent ratiometric probe Fura-2, however, a protein kinase C inhibitor (GF109203x) blocked the C1q-induced P-selectin expression. Furthermore, pre-incubation of platelets with C1q diminished both the collagen as well as the collagen-related peptide-induced up-regulation of P-selectin, most evident after 90 s of stimulation. This indicates that C1q may regulate platelet activation via the GPVI receptor, which is a novel finding. Moreover, C1q antagonized the collagen-induced formation of platelet-neutrophil aggregates, indicating a reduced interaction between platelet P-selectin and neutrophil P-selectin glycoprotein ligand-1(PSGL-1/CD162). In summary, C1q induces a moderate rapid platelet P-selectin expression, modulates subsequent collagen and collagen-related peptide stimulation of platelets, and inhibits the formation of platelet-neutrophil aggregates. These immuno-regulatory effects of C1q may have a crucial role in innate immunity and inflammation. (C) 2009 Elsevier GmbH. All rights reserved.
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| 47. |
- Sundström, Christer, et al.
(författare)
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Patients with autoimmune diseases have an altered activity of the PD-1 pathway and proportions of Epstein-Barr virus infected cells in benign lymphadenopathies
- 2021
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Ingår i: Immunobiology. - : Elsevier. - 0171-2985 .- 1878-3279. ; 226:2
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Tidskriftsartikel (refereegranskat)abstract
- Patients with autoimmune diseases (AD) have an increased risk to develop benign lymphadenopathies compared to patients without AD. The aim with this study was to determine the role of the PD-1 pathway and the number of cells harboring Epstein-Barr virus (EBV) in benign lymphadenopathies in patients with AD (cases) compared to patients without AD (controls). Pathology registries were screened to identify patients with biopsies diagnosed as benign lymphadenopathy and medical journals were reviewed for information on AD. Immunohistochemical stainings (PD-1 and PD-L1) and EBER in situ hybridization for EBV were applied on lymph node biopsies in patients with AD (n = 22) and patients without AD (n = 57). The case group was compared with the control group with Wilcoxon-signed rank, chi-square and Fischers exact test. There was a statistically significantly higher proportion of PD-1+ cells and a tendency for a lower prevalence of PD-L1+ and EBV+ cells in cases compared to controls. Apparently, patients with AD have an altered immune response as revealed in benign lymphadenopathies compared to patients without AD. If this association might be a piece of the puzzle for the increased risk of development of lymphomas in patients with AD remains to be determined.
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| 48. |
- Svärd, Anna, et al.
(författare)
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Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis
- 2013
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Ingår i: Immunobiology. - : Elsevier. - 0171-2985 .- 1878-3279. ; 218:2, s. 232-237
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Tidskriftsartikel (refereegranskat)abstract
- Circulating IgG anti-cyclic citrullinated peptide antibodies (CCP) are highly specific for rheumatoid arthritis (RA) and prognostic of poor outcome. Serum IgA anti-CCP occurs in a subset of IgG-positive cases and relates to still more aggressive disease. Mucosal IgA-class antibodies, however, are generally associated with anti-inflammatory actions and systemic tolerance induction. In the present study, unstimulated salivary samples from 63 patients with established RA and 20 healthy persons were analysed by enzyme-linked immunoassay for the presence of IgA anti-CCP antibodies. To ensure antigen specificity, IgA-reactivity with the corresponding uncitrullinated antigen, cyclic arginine peptide (CAP), was analysed and anti-CCP/anti-CAP ratios calculated. Retrospective data regarding disease activity and radiological outcome were achieved via medical records. Salivary IgA anti-CCP was found in 14/63 (22%) patients and one (5%) control (positive test = anti-CCP/anti-CAP ratio andgt; 1.5). Salivary IgA reactivity was dose-dependently inhibited by pre-incubation with soluble CCP to a degree strongly correlating with anti-CCP/anti-CAP ratio. In salivary IgA anti-CCP positive patients, joint erosions within 6 years of diagnosis was significantly lower (p = 0.043), and at the time for diagnosis there was a trend towards lower erythrocyte sedimentation rate (p = 0.071) and C-reactive protein (p = 0.085). Contrasting to circulating IgG and IgA anti-CCP, our results imply that salivary IgA antibodies may be associated with a less severe outcome of RA. Hypothetically, this relates to an anti-inflammatory and protective immunomodulating role of secretory IgA-class autoantibodies against citrullinated antigens presented at mucosal surfaces.
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