| 1. |
- Ankarklev, Johan, et al.
(författare)
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Behind the smile : cell biology and disease mechanisms of Giardia species
- 2010
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Ingår i: Nature Reviews Microbiology. - : Springer Science and Business Media LLC. - 1740-1526 .- 1740-1534. ; 8:6, s. 413-422
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Forskningsöversikt (refereegranskat)abstract
- The eukaryotic intestinal parasite Giardia intestinalis was first described in 1681, when Antonie van Leeuwenhoek undertook a microscopic examination of his own diarrhoeal stool. Nowadays, although G. intestinalis is recognized as a major worldwide contributor to diarrhoeal disease in humans and other mammals, the disease mechanisms are still poorly understood. Owing to its reduced complexity and proposed early evolutionary divergence, G. intestinalis is used as a model eukaryotic system for studying many basic cellular processes. In this Review we discuss recent discoveries in the molecular cell biology and pathogenesis of G. intestinalis.
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| 2. |
- Evren, Elza, et al.
(författare)
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Distinct developmental pathways from blood monocytes generate human lung macrophage diversity
- 2021
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Ingår i: Immunity. - : Elsevier. - 1074-7613 .- 1097-4180. ; 51, s. 35-35
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Tidskriftsartikel (refereegranskat)abstract
- The study of human macrophages and their ontogeny is an important unresolved issue. Here, we use a humanized mouse model expressing human cytokines to dissect the development of lung macrophages from human hematopoiesis in vivo. Human CD34+ hematopoietic stem and progenitor cells (HSPCs) generated three macrophage populations, occupying separate anatomical niches in the lung. Intravascular cell labeling, cell transplantation, and fate-mapping studies established that classical CD14+ blood monocytes derived from HSPCs migrated into lung tissue and gave rise to human interstitial and alveolar macrophages. In contrast, non-classical CD16+ blood monocytes preferentially generated macrophages resident in the lung vasculature (pulmonary intravascular macrophages). Finally, single-cell RNA sequencing defined intermediate differentiation stages in human lung macrophage development from blood monocytes. This study identifies distinct developmental pathways from circulating monocytes to lung macrophages and reveals how cellular origin contributes to human macrophage identity, diversity, and localization in vivo.
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| 3. |
- Hanevik, Kurt, et al.
(författare)
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Human Cellular Immune Response Against Giardia lamblia 5 Years After Acute Giardiasis
- 2011
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 204:11, s. 1779-1786
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Tidskriftsartikel (refereegranskat)abstract
- Background. Clinical and epidemiological studies have suggested the development of acquired immunity in individuals previously infected with Giardia lamblia. However, there are no data on the long-term cellular immunity and genotype cross-reactivity. An outbreak of assemblage B giardiasis in a nonendemic area made it possible to evaluate the long-term cellular mediated immunity and its specificity toward the 2 Giardia assemblages known to infect humans. Methods. Peripheral blood mononuclear cells from 19 individuals infected with Giardia assemblage B 5 years previously and from 10 uninfected controls were cultured with antigens from assemblage A and B Giardia trophozoites for 6 days. Cell-mediated immunity was measured by a (3)H-thymidine proliferation assay and flow cytometric analysis of activation markers HLA-DR, CD45RO, CD25, and CD26 in T-cell subsets. Results. Proliferation responses were significantly elevated in the group previously exposed to Giardia for nearly all Giardia antigens tested. Individual responses toward Giardia trophozoite whole cell, cytosolic, and excretory-secretory antigens from both assemblages correlated well. Activation marker responses were mainly seen in CD4 T cells. Conclusions. G. lamblia infection induces long-term, albeit variable, cellular immune responses that are not assemblage specific and that are largely driven by CD4 T-cell activation.
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| 4. |
- Kvedaraite, Egle, et al.
(författare)
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Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA+CD142−/low fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRA+CD142−/low fibroblasts foster monocyte transition to CCR2+CD206+ macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2+CD206+ cells from co-cultures have a phenotype similar to intestinal CCR2+CD206+ macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation.
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| 5. |
- Ringqvist, Emma, 1979-
(författare)
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Host-Pathogen Responses during Giardia infections
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Giardia lamblia is a eukaryotic parasite of the upper small intestine of humans and animals. The infecting trophozoite cells do not invade the epithelium lining of the intestine, but attach to the brush border surface in the intestinal lumen. The giardiasis disease in humans is highly variable. Prior to this study, the molecular mechanisms involved in establishment of infection or cause of disease were largely uncharacterized. In this thesis, the molecular relationship between Giardia and the human host is described. The interaction of the parasite with human epithelial cells was investigated in vitro. Changes in the transcriptome and proteome of the parasite and the host cells, and changes in the micro-environment of the infection have been identified using microarray technology, and 1- and 2-Dimensional SDS-PAGE protein mapping together with mass spectrometry identification. The first large-scale description of cellular activities within host epithelial cells during Giardia infection is included in this thesis (Paper I). We identified a unique activation of the host immune response and induction of apoptosis upon infection by Giardia. Four important virulence factors of the parasite, directly linked to the success of Giardia infection, were characterized and are presented in Papers II and III. The parasite was shown to have immune-modulating capacities, and to release proteins during host-interaction that facilitate the establishment of infection. Additional putative virulence factors were found among Giardia genes transcriptionally up-regulated during early infection (Paper IV). In summary, this thesis provides important insights into the molecular mechanisms of the host-parasite interaction.
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| 6. |
- Ringqvist, Emma, et al.
(författare)
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Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells
- 2008
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Ingår i: Molecular and biochemical parasitology (Print). - : Elsevier BV. - 0166-6851 .- 1872-9428. ; 159:2, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Giardia lamblia, an important cause of diarrheal disease, resides in the small intestinal lumen in close apposition to epithelial cells. Since the disease mechanisms underlying giardiasis are poorly understood, elucidating the specific interactions of the parasite with the host epithelium is likely to provide clues to understanding the pathogenesis. Here we tested the hypothesis that contact of Giardia lamblia with intestinal epithelial cells might lead to release of specific proteins. Using established co-culture models, intestinal ligated loops and a proteomics approach, we identified three G. lamblia proteins (arginine deiminase, ornithine carbamoyl transferase and enolase), previously recognized as immunodominant antigens during acute giardiasis. Release was stimulated by cell-cell interactions, since only small amounts of arginine deiminase and enolase were detected in the medium after culturing of G. lamblia alone. The secreted G. lamblia proteins were localized to the cytoplasm and the inside of the plasma membrane of trophozoites. Furthermore, in vitro studies with recombinant arginine deiminase showed that the secreted Giardia proteins can disable host innate immune factors such as nitric oxide production. These results indicate that contact of Giardia with epithelial cells triggers metabolic enzyme release, which might facilitate effective colonization of the human small intestine.
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| 7. |
- Ringqvist, Emma, 1979-, et al.
(författare)
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Transcriptional changes in Giardia during host-parasite interactions
- 2011
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Ingår i: International Journal for Parasitology. - : Elsevier BV. - 0020-7519 .- 1879-0135. ; 41:3-4, s. 277-285
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Tidskriftsartikel (refereegranskat)abstract
- Giardia intestinalis is one of the major causes of parasite-induced diarrhea. The disease, giardiasis, is caused by trophozoites attaching to the intestinal epithelium, resulting in apoptosis of intestinal epithelial cells, disrupted epithelial barrier function and malabsorption. Microarray studies have detected gene expression changes in intestinal epithelial cells (IECs), during interaction with Giardia trophozoites in vitro. In the present study we examined this host-parasite interaction further by transcriptional profiling of interacting trophozoites using Giardia oligo microarrays. A total of 325 Giardia transcripts were significantly changed during the interaction, lasting 1.5 to 18 hrs in complete DMEM medium. Quantitative real-time reverse transcriptase PCR confirmed these changes in all 12 genes tested using mRNA isolated in a separate experiment. Genes involved in cell division and attachment were down-regulated in the late time-points of interaction. Proteins earlier suggested to be important during host parasite interactions like arginine deiminase and cysteine proteinases changed their expression. Oxygen defense proteins and several members of the high cysteine-rich membrane protein (HCMp) family were up-regulated during the interaction with IECs. Thus, there are extensive gene-expression changes in Giardia trophozoites and IECs during host-parasite interactions and this can be important for establishment of infection and in the induction of giardiasis.
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| 8. |
- Roxström-Lindquist, Katarina, et al.
(författare)
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Giardia immunity--an update.
- 2006
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Ingår i: Trends Parasitol. - : Elsevier BV. - 1471-4922. ; 22:1, s. 26-31
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
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| 10. |
- Skarin, Hanna, et al.
(författare)
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Elongation factor 1-alpha is released into the culture medium during growth of Giardia intestinalis trophozoites
- 2011
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Ingår i: Experimental parasitology. - : Elsevier BV. - 0014-4894 .- 1090-2449. ; 127:4, s. 804-810
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Tidskriftsartikel (refereegranskat)abstract
- The molecular pathogenesis of the intestinal parasite Giardia intestinalis is still not fully understood but excretory-secretory products have been suggested to be important during host-parasite interactions. Here we used SOS-PAGE gels and MALDI-TOF analysis to identify proteins released by Giardia trophozoites during in vitro growth. Serum proteins (mainly bovine serum albumin) in the growth medium, bind to the parasite surface and they are continuously released, which interfere with parasite secretome characterization. However, we identified two released Giardia proteins: elongation factor-1 alpha (EF-1 alpha) and a 58 kDa protein, identified as arginine deiminase (ADI). This is the first description of EF-1 alpha as a released/secreted Giardia protein, whereas ADI has been identified in an earlier secretome study. Two genes encoding EF-1 alpha were detected in the Giardia WB genome 35 kbp apart with almost identical coding sequences but with different promoter and 3' regions. Promoter luciferase-fusions showed that both genes are transcribed in trophozoites. The EF-1 alpha protein localizes to the nuclear region in trophozoites but it relocalizes to the cytoplasm during host-cell interaction. Recombinant EF-1 alpha is recognized by serum from giardiasis patients. Our results suggest that released EF-1 alpha protein can be important during Giardia infections.
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