Immunological consequence of alcohol consumption on mucosa derived CD4+ T cell phenotype and In Vitro susceptibility to HIV-1 infection.

Abstract

In Sub-Saharan Africa, there is a significant over-lap in Alcohol use disorder and HIV infection burden and about 60% of the HIV infections occur in women. Alcohol exerts several modulatory effects on the immune system such as altered cell surface receptor expression, mucosal barrier breach, inflammatory responses and lymphocyte homing. Due to the high absorptive property of alcohol into the systemic circulation, alcohol-induced immune modulatory effects are exerted throughout the body including the the vaginal mucosa and this may enhance initial HIV-1infection. Despite evidence of modulatory effect of alcohol consumption on peripheral blood derived T cells that potentially increase susceptibility to HIV infection, a substantial knowledge gap still exists on the effect of alcohol consumption on genital/vaginal CD4+T cells which are the initial targets for HIV infection establishment on sexual exposure. The knowledge generated from this study is crucial for development of HIV/AIDS preventive and therapeutic strategies that target the genital mucosa as well as advocate for integration of alcohol abuse control in HIV/AIDS programs. Therefore, this study aimed to investigate the immunological consequence of alcohol consumption on Mucosal CD4+ cells and In Vitro susceptibility to HIV-1 infection. Methods: This was a cross-sectional study. Cervical Cytobrush and venous blood samples were collected from 52 HIV-negative women aged 18-49 years old. HIV sero-positive and Pregnant women were excluded. Data on alcohol use was captured using the standard WHO-AUDIT questionnaire and categorized as prescribed by the tool. Isolated Cervical and peripheral blood mononuclear cells were surface stained for CD4+ T cell immuno-phenotyping and exposed to equal Green-fluorescent-protein tagged HIV-1 pseudo-virus particles to measure susceptibility to HIV entry by flow cytometric determination of number of GFP+ positive cells in the total events acquired. Results: Both alcohol- and non-alcohol consumer study groups exhibited similar demographic characteristics and majority did not report genital tract infections at time of sample collection. On analysis of the cervical CD4+ T cell phenotype frequencies, we found no significant difference(p=0.4514)between the two study groups. However, HIV entry was two-fold higher (P=0.0185) in cervical CD4+ T cells from alcohol consumers than in non-alcohol consumers. Cervical CD4+α4β7+T cells in alcohol consumers were four-fold more susceptible to HIV-1 entry than other cervical CD4+T cell phenotypes. Conclusion: This study demonstrates that cervical CD4+ T cells from alcohol consumers are more susceptible to HIV entry than those in non-alcohol consumers. We also demonstrate that cervical CD4+ T cells exhibit increased susceptibility to HIV entry compared to peripheral derived CD4+ T cells. Interestingly, α4β7 expressing cervical CD4+ T cells from alcohol consumers were found to be more susceptible to HIV entry than those in non-alcohol consumers. However, we recommend further studies with a larger sample to validate the findings in this study.