| 1. |
- Boraschi, Diana, et al.
(författare)
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Immunity against HIV/AIDS, malaria, and tuberculosis during co-infections with neglected infectious diseases: recommendations for the European Union research priorities.
- 2008
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Ingår i: PLoS neglected tropical diseases. - : Public Library of Science (PLoS). - 1935-2735. ; 2:6
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Tidskriftsartikel (refereegranskat)abstract
- Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB) have received most of the world's attention. However, in rural and impoverished urban areas, a number of infectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are either not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9-11, 2007. The message coming from these scientists is that the only possibility for winning the fight against infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective.
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| 2. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Markers of immune stimulation in the cerebrospinal fluid during HIV infection: a longitudinal study
- 1994
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Ingår i: Scand J Infect Dis. - : Informa UK Limited. ; 26:5, s. 523-33
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Tidskriftsartikel (refereegranskat)abstract
- Markers of immune stimulation were studied in 76 sequential cerebrospinal fluid (CSF) samples from 19 patients infected with HIV-1 without antiretroviral treatment during observation periods ranging from 22 months to 6 years. Eight of these patients were further followed with 14 CSF samples for 3-24 months of zidovudine treatment. During the course of HIV-1 infection, the mean CSF neopterin and beta 2-microglobulin (beta 2M) concentrations increased from 12.7 to 20.4 nmol/l (p < 0.01) and from 1.93 to 2.17 mg/l (p < 0.05), respectively, while the mean peripheral CD4 + T cell count decreased from 624 to 320 cells x 10(6)/l (p < 0.001). The IgG index, reflecting intrathecal immunoglobulin production, increased from 0.72 to 0.92 (p = 0.08). The number of patients with CSF pleocytosis did not change significantly during follow-up (8/19 at baseline, 7/19 at endpoint). In the 8 patients followed up during antiretroviral treatment, a significant reduction in mean CSF levels of neopterin and beta 2M (-48% and -32%, respectively, p < 0.01) was seen after 3-12 months on zidovudine. We suggest that gradual increase in immune stimulation reflected by the rising CSF concentrations of neopterin and beta 2M indicates that HIV-1 infection in the central nervous system is progressive even in neurologically asymptomatic stages.
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| 3. |
- Kiene, Miriam, et al.
(författare)
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Toll-Like Receptor 3 Signalling Up-Regulates Expression of the HIV Co-Receptor G-Protein Coupled Receptor 15 on Human CD4(+) T Cells.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Many HIV-2 and SIV isolates, as well as some HIV-1 strains, can use the orphan 7-transmembrane receptor GPR15 as co-receptor for efficient entry into host cells. GPR15 is expressed on central memory and effector memory CD4(+) T cells in healthy individuals and a subset of these cells is susceptible to HIV-1 and SIV infection. However, it has not been determined whether GPR15 expression is altered in the context of HIV-1 infection.
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| 4. |
- Martinson, Neil, et al.
(författare)
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Proteomic Analysis of Mucosal and Systemic Responses to SARS-CoV-2 Antigen
- 2023
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Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- The mucosal environment of the upper respiratory tract is the first barrier of protection against SARS-CoV-2 transmission. However, the mucosal factors involved in viral transmission and potentially modulating the capacity to prevent such transmission have not fully been identified. In this pilot proteomics study, we compared mucosal and systemic compartments in a South African cohort of vaccinated and unvaccinated individuals undergoing maxillofacial surgery with previous history of COVID-19 or not. Inflammatory profiles were analyzed in plasma, nasopharyngeal swabs, and nasal and oral tissue explant cultures, using Olink and Luminex technologies. SARS-CoV-2-specific antibody levels were measured in serum and tissue explants. An increased pro-inflammatory proteomic profile was measured in the nasal compartment compared to plasma. However, IP-10 and MIG levels were higher in secretions than in nasal tissue, and the opposite was observed for TGF-beta. Nasal anti-SARS-CoV-2 spike IgG correlated with mucosal MIG expression for all participants. A further positive correlation was found with IP-10 in BioNTech/Pfizer-vaccinated individuals. Systemic levels of anti-SARS-CoV-2 spike IgG elicited by this vaccine correlated with plasma IL-10, IL-6 and HBD4. Proteomic profiles measured in mucosal tissues and secretions using combined technologies could reveal correlates of protection at the mucosal portals of viral entry.
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| 5. |
- Nasi, Aikaterini, et al.
(författare)
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Dendritic cell response to HIV-1 is controlled by differentiation programs in the cells and strain-specific properties of the virus
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8:MAR
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells. By exploiting this mechanism, we generated immunostimulatory DCs characterized by the production of TH1 polarizing and inflammatory mediators or, alternatively, suppressed DCs that produce IL-10 upon activation, and we tested the interaction of these DC types with different HIV-1 strains. Cytokine patterns were monitored in HIV-1-exposed DC cultures. Our results showed that DCs receiving suppressive developmental program strongly upregulated their capacity to produce the TH1 polarizing cytokine IL-12 and the inflammatory chemokines CCL2 and CCL7 upon interaction with HIV-1 strains IIIB and SF162. On the contrary, HIV-1 abolished cytokine production in the more inflammatory DC types. Preincubation of the cells with the HIV-1 proteins gp120 and Nef could inhibit IL-12 production irrespectively of the tested DC types, whereas MyD88- and TRIF-dependent signals stimulated IL-12 production in the suppressed DC type only. Rewiring of DC cytokines did not require DC infections or ligation of the HIV-1 receptor CD209. A third HIV-1 strain, BaL, could not modulate DC cytokines in a similar manner indicating that individual HIV-1 strains can differ in their capacity to influence DCs. Our results demonstrated that HIV-1 could not induce definite and invariable modulatory programs in DCs. Instead, interaction with the virus triggered different responses in different DC types. Thus, the outcome of DC-HIV-1 interactions might be highly variable, shaped by endogenous features of the cells and diversity of the virus.
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| 6. |
- Reddy, Sreenivasulu B., et al.
(författare)
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Direct contact between Plasmodium falciparum and human B-cells in a novel co-culture increases parasite growth and affects B-cell growth
- 2021
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Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Plasmodium falciparum parasites cause malaria and co-exist in humans together with B-cells for long periods of time. Immunity is only achieved after repeated exposure. There has been a lack of methods to mimic the in vivo co-occurrence, where cells and parasites can be grown together for many days, and it has been difficult with long time in vitro studies. Methods and results: A new method for growing P. falciparum in 5% CO2 with a specially formulated culture medium is described. This knowledge was used to establish the co-culture of live P. falciparum together with human B-cells in vitro for 10 days. The presence of B-cells clearly enhanced parasite growth, but less so when Transwell inserts were used (not allowing passage of cells or merozoites), showing that direct contact is advantageous. B-cells also proliferated more in presence of parasites. Symbiotic parasitic growth was verified using CESS cell-line and it showed similar results, indicating that B-cells are indeed the cells responsible for the effect. In malaria endemic areas, people often have increased levels of atypical memory B-cells in the blood, and in this assay it was demonstrated that when parasites were present there was an increase in the proportion of CD19 + CD20 + CD27 − FCRL4 + B-cells, and a contraction of classical memory B-cells. This effect was most clearly seen when direct contact between B-cells and parasites was allowed. Conclusions: These results demonstrate that P. falciparum and B-cells undoubtedly can affect each other when allowed to multiply together, which is valuable information for future vaccine studies.
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| 7. |
- Sabri, Farideh, et al.
(författare)
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Soluble factors released by virus specific activated cytotoxicT-lymphocytes induce apoptotic death of astroglioma cell lines
- 2003
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Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 13:2, s. 165-175
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytomas and astrogliomas represent the most common types of primary tumors in human central nervous system and are associated with high mortality due to the absence of efficient therapy. Here we demonstrate that, upon antigen-specific activation, cytotoxic T-lymphocytes (CTLs) secrete products that inhibit proliferation and induce apoptosis in a significant proportion of astroglioma cell lines. This effect is tumor specific in that normal cultured astrocytes do not develop apoptotic changes upon exposure to supernatant of activated CTLs. Experiments with purified lymphokines and lymphokine specific blocking antibodies indicate that synergistic activities of tumor necrosis factor (TNF)-alpha and interferon (INF)-gamma are required for the apoptosis inducing effect on some astroglioma cell lines. However, this effect appears to be dependent on additional factors produced by activated CTLs. Our results suggest that local application of factors released by activated CTLs or induction of CTL migration and activation in the tumor site may have a therapeutic effect in patients with astrogliomas.
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| 8. |
- Sahi, Maryam, et al.
(författare)
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Profiling of Surface Protein Epitopes on Viral Particles by Multiplex Dual-Reporter Strategy
- 2024
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Ingår i: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; 2024:203
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Tidskriftsartikel (refereegranskat)abstract
- Membrane proteins on enveloped viruses play an important role in many biological functions involving virus attachment to target cell receptors, fusion of viral particles to host cells, host-virus interactions, and disease pathogenesis. Furthermore, viral membrane proteins on virus particles and presented on host cell surfaces have proven to be excellent targets for antivirals and vaccines. Here, we describe a protocol to investigate surface proteins on intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particles using the dual-reporter flow cytometric system. The assay exploits multiplex technology to obtain a triple detection of viral particles by three independent affinity reactions. Magnetic beads conjugated to recombinant human angiotensin-converting enzyme-2 (ACE2) were used to capture viral particles from the supernatant of cells infected with SARS-CoV-2. Then, two detection reagents labeled with R-phycoerythrin (PE) or Brilliant Violet 421 (BV421) were applied simultaneously. As a proof-of-concept, antibody fragments targeting different epitopes of the SARS CoV-2 surface protein Spike (S1) were used. The detection of viral particles by three independent affinity reactions provides strong specificity and confirms the capture of intact virus particles. Dose-dependency curves of SARS-CoV-2 infected cell supernatant were generated with replicate coefficient variances (mean/SD) ˂14%. Good assay performance in both channels confirmed that two virus surface target protein epitopes are detectable in parallel. The protocol described here could be applied for (i) high-multiplex, high-throughput profiling of surface proteins expressed on enveloped viruses; ii) detection of active intact viral particles; and (iii) assessment of specificity and affinity of antibodies and antiviral drugs for surface epitopes of viral antigens.The application can be potentially extended to any type of extracellular vesicles and bioparticles, exposing surface antigens in body fluids or other liquid matrices.
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