CD4+ CD25High Treg cells in HIV/HTLV Co-infected patients with neuropathy: high expression of Alpha4 integrin and lower expression of Foxp3 transcription factor

Submitted by sandra infurna ([email protected]) on 2016-03-08T12:22:28Z No. of bitstreams: 1 wilson_savino_etal_IOC_2015.pdf: 718610 bytes, checksum: e5567ab75523b3c84f56fec19abe6671 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-03-08T14:26:31Z (GMT) No. of bitstreams: 1 wilson_savino_etal_IOC_2015.pdf: 718610 bytes, checksum: e5567ab75523b3c84f56fec19abe6671 (MD5)Made available in DSpace on 2016-03-08T14:26:31Z (GMT). No. of bitstreams: 1 wilson_savino_etal_IOC_2015.pdf: 718610 bytes, checksum: e5567ab75523b3c84f56fec19abe6671 (MD5) Previous issue date: 2015Ministry of Health. National Institute of Health. Maputo, Mozambique.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Ministry of Health. National Institute of Health. Maputo, Mozambique.Ministry of Health. National Institute of Health. Maputo, Mozambique.Ministry of Health. National Institute of Health. Maputo, Mozambique.Ministry of Health. National Institute of Health. Maputo, Mozambique.Ministry of Health. National Institute of Health. Maputo, Mozambique.Ministry of Health. National Institute of Health. Maputo, Mozambique.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Background: Regulatory CD4 T cells (Tregs) are critical in maintaining the homeostasis of the immune system. Quantitative or phenotypic alterations and functional impairment of Tregs have been associated with the development of pathologies including those of the central nervous system. Individuals with HIV-1/HTLV-1 co-infection are more prone to develop neurological complications. The aim of this study was to characterize phenotypically Treg cells in HIV-1/HTLV-1 co-infected Mozambican individuals presenting neurological symptoms. Methods: A cross-sectional study was conducted among HIV-infected individuals presentingneurological symptoms, with and without HTLV co-infection, and blood donors. Peripheral bloodmononuclear cells were stained with monoclonal antibodies conjugated with fluorochromes to quantifyTregs and activated T cells by four colors flow cytometry. Results: Higher Treg cell frequency (10.6 %) was noted in HIV-1/HTLV-1 co-infected group with neurological symptoms when compared to HIV-1 mono-infected group with neurological symptoms (0.38 %, p = 0.003) and control group (0.9 %, p = 0.0105). An inverse correlation between Foxp3 and CD49d expression was observed in all study groups (rh = −0.71, p = 0.001). In addition, increased levels of Treg cells in co-infected patients were strongly associated with total activated CD4 T cells (rh = 0.8, p = 0.01). Conclusion: Treg cells in co-infected patients present phenotypic alterations and might have dysfunction marked by low expression of Foxp3 and increased expression of molecules not frequently seen on Treg cells, such as CD49d. These alterations may be related to (1) changes in Treg cell trafficking and migration, possibly making those cells susceptible to HIV infection, and (2) inability to control the activation and proliferation of effector T lymphocytes

Vaccine-Induced Seroreactivity Impacts the Accuracy of HIV Testing Algorithms in Sub-Saharan Africa: An Exploratory Study

The detection of vaccine-induced HIV antibody responses by rapid diagnostic tests (RDTs) may confound the interpretation of HIV testing results. We assessed the impact of vaccine-induced seroreactivity (VISR) on the diagnosis of HIV in sub-Saharan Africa. Samples collected from healthy participants of HIVIS and TaMoVac HIV vaccine trials after the final vaccination were analyzed for VISR using HIV testing algorithms used in Mozambique and Tanzania that employ two sequential RDTs. The samples were also tested for VISR using Enzygnost HIV Integral 4 ELISA and HIV western blot assays. Antibody titers to subtype C gp140 were determined using an in-house enzyme-linked immunosorbent assay (ELISA). The frequency of VISR was 93.4% (128/137) by Enzygnost HIV Integral 4 ELISA, and 66.4% (91/137) by western blot assay (WHO interpretation). The proportion of vaccine recipients that would have been misdiagnosed as HIV-positive in Mozambique was half of that in Tanzania: 26.3% (36/137) and 54.0% (74/137), respectively, p < 0.0001. In conclusion, the HIV RDTs and algorithms assessed here will potentially misclassify a large proportion of the HIV vaccine recipients if no other test is used. Increased efforts are needed to develop differential serological or molecular tools for use at the point of care

Helios expressing regulatory T cells are correlated with decreased IL-2 producing CD8 T cells and antibody diversity in Mozambican individuals living chronically with HIV-1

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) causes impairment of T and B cell responses, which begins during the acute phase of infection and is not completely restored by antiretroviral treatment. Regulatory T cell (Tregs) can improve overall disease outcome by controlling chronic inflammation but may also suppress beneficial HIV-1 specific immune responses. We aimed to analyze the profile of Tregs and their correlation with the status of T cells activation, the expression of IL-2 and IFNγ and the profile of HIV-1 specific antibodies response in Mozambican people living chronically with HIV-1 (PLWH-C). RESULTS: In PLWH-C, the proportion of total Tregs was positively correlated with the proportion of IL-2(+)CD4 T cells (r = 0.647; p = 0.032) and IL-2(+)IFNγ(+)CD8 T cells (r = 0.551; p = 0.014), while the proportions of Helios(+)Tregs correlated inversely with levels of IL-2(+)CD8 T cells (r = − 0.541; p = 0.017). Overall, PLWH-C, with (82%) or without virologic suppression (64%), were seronegative for at least HIV-1 p31, gp160 or p24, and the breadth of antibody responses was positively correlated with proportions of CD38(+)HLA-DR(+)CD8 T cells (r = 0.620; p = 0.012), viral load (r = 0.452; p = 0.040) and inversely with absolute CD4 T cells count (r = − 0.481; p = 0.027). Analysis of all individuals living HIV-1 showed that the breadth of HIV-1 antibody responses was inversely correlated with the proportion of Helios(+)Tregs (r = − 0.45; p = 0.02). CONCLUSION: Among Mozambican people living with HIV-1, seronegativity to some HIV-1 proteins is common, particularly in virologically suppressed individuals. Furthermore, lower diversity of HIV-specific antibodies is correlated to lower immune activation, lower viral replication and higher CD4 counts, in PLWH-C. Elevation in the proportion of Helios(+)Tregs is related to a reduction of CD8 T expressing intracellular IL-2, in PLWH-C, but may contribute to impairment of B cell function. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12865-022-00487-3

Tuberculosis Treatment Response Monitoring by the Phenotypic Characterization of <em>MTB</em>-Specific <em>CD4+</em> T-Cells in Relation to HIV Infection Status

HIV infection causes systemic immune activation, impacts TB disease progression and hence may influence the diagnostic usability of Mycobacterium tuberculosis-specific T cell profiling. We investigated changes of activation and maturation markers on MTB-specific CD4+ T-cells after anti-tuberculosis treatment initiation in relation to HIV status and the severity of lung impairment. Thawed peripheral blood mononuclear cells from TB patients with (n = 27) and without HIV (n = 17) were analyzed using an intracellular IFN-γ assay and flow cytometry 2 and 6 months post-TB treatment initiation. H37Rv antigen was superior to the profile MTB-specific CD4+ T-cells phenotype when compared to PPD and ESAT6/CFP10. Regardless of HIV status and the severity of lung impairment, activation markers (CD38, HLA-DR and Ki67) on MTB-specific CD4+ T-cells declined after TB treatment initiation (p MTB-specific T cell phenotype before, during and after treatment completion was similar between people living with and without HIV, as well as between subjects with severe and mild lung impairment. These data suggest that the assessment of activation and maturation markers on MTB-specific CD4+ T-cells can be useful for TB treatment monitoring, regardless of HIV status and the severity of lung disease

Effect of TB Treatment on Neutrophil-Derived Soluble Inflammatory Mediators in TB Patients with and without HIV Coinfection

The mycobacteriological analysis of sputum samples is the gold standard for tuberculosis diagnosis and treatment monitoring. However, sputum production can be challenging after the initiation of TB treatment. As a possible alternative, we therefore investigated the dynamics of neutrophil-derived soluble inflammatory mediators during TB treatment in relation to HIV ART status and the severity of lung impairment. Plasma samples of TB patients with (N = 47) and without HIV (N = 21) were analyzed at baseline, month 2, month 6 (end of TB treatment) and month 12. Plasma levels of MMP-1, MMP-8, MPO and S100A8 markedly decreased over the course of TB treatment and remained at similar levels thereafter. Post-TB treatment initiation, significantly elevated plasma levels of MMP-8 were detected in TB patients living with HIV, especially if they were not receiving ART treatment at baseline. Our data confirm that the plasma levels of neutrophil-based biomarkers can be used as candidate surrogate markers for TB treatment outcome and HIV-infection influenced MMP-8 and S100A8 levels. Future studies to validate our results and to understand the dynamics of neutrophils-based biomarkers post-TB treatment are needed

HIV prevalence and risk behavior among male and female adults screened for enrolment into a vaccine preparedness study in Maputo, Mozambique.

IntroductionMozambique continues to have a significant burden of HIV. Developing strategies to control the HIV epidemic remains a key priority for the Mozambican public health community. The primary aim of this study was to determine HIV prevalence and risk behavior among males and females screened for a HIV vaccine preparedness study in Maputo, Mozambique.MethodsMale and female participants between 18-35 years old were recruited from the general community and from female sex worker (FSW) and lesbian, gay, bisexual, and transgender (LGBT) associations in Maputo. All participants were screened for HIV and a questionnaire was administered to each participant to assess HIV risk behavior.ResultsA total of 1125 adults were screened for HIV infection, among whom 506 (45%) were male. Among men, 5.7% reported having had sex with men (MSM) and 12% of female participants reported having exchanged sex for money, goods or favors in the past 3 months. The overall HIV prevalence was 10.4%; 10.7% of women, and 10.1% of men were HIV infected; 41.4% of MSM were seropositive. HIV infection was associated with older age (25-35 years old) (OR: 6.13, 95% CI: 3.01, 12.5), MSM (OR: 9.07, 95% CI: 3.85, 21.4), self-perception of being at high-risk for HIV (OR: 3.99, 95% CI: 1.27, 12.5) and self-report of a history of a diagnosis of sexually transmitted infection (OR: 3.75, 95% CI: 1.57, 8.98).ConclusionIn our cohort, HIV prevalence was much higher among MSM compared to the overall prevalence. Behavioral factors were found to be more associated with HIV prevalence than demographic factors. The study findings demonstrate the critical importance of directing services to minority communities, such as MSM, when prevention strategies are being devised for the general population

L'Avenir de Luchon : journal scientifique, littéraire, annonces et réclames : guide général des baigneurs et des touristes aux eaux thermales, bains de mer de la France et de l'étranger

08 janvier 19331933/01/08 (N573)-1933/01/08.Appartient à l’ensemble documentaire : MidiPyren

Determining hematological, biochemical and immunological reference values in healthy adults with high-risk for HIV acquisition in Mozambique.

INTRODUCTION:In many African countries, laboratory reference values are not established for the local healthy adult population. In Mozambique, reference values are known for young adults (18-24yo) but not yet established for a wider age range. Our study aimed to establish hematological, biochemical and immunological reference values for vaccine trials in Mozambican healthy adults with high-risk for HIV acquisition. METHODS:A longitudinal cohort and site development study in Mozambique between November 2013 and 2014 enrolled 505 participants between 18 to 35 years old. Samples from these healthy participants, were analyzed to determine reference values. All volunteers included in the analysis were clinically healthy and human immunodeficiency virus (HIV), hepatitis B and C virus, and syphilis negative. Median and reference ranges were calculated for the hematological, biochemical and immunological parameters. Ranges were compared with other African countries, the USA and the US National Institute of Health (NIH) Division of AIDS (DAIDS) toxicity tables. RESULTS:A total of 505 participant samples were analyzed. Of these, 419 participants were HIV, hepatitis B and C virus and syphilis negative including 203 (48.5%) females and 216 (51.5%) males, with a mean age of 21 years. In the hematological parameters, we found significant differences between sex for erythrocytes, hemoglobin, hematocrit, MCV, MCH and MCHC as well as white blood cells, neutrophils and platelets: males had higher values than females. There were also significant differences in CD4+T cell values, 803 cells/μL in men versus 926 cells/μL in women. In biochemical parameters, men presented higher values than women for the metabolic, enzymatic and renal parameters: total and direct bilirubin, ALT and creatinine. CONCLUSION:This study has established reference values for healthy adults with high-risk for HIV acquisition in Mozambique. These data are helpful in the context of future clinical research and patient care and treatment for the general adult population in the Mozambique and underline the importance of region-specific clinical reference ranges