Poverty and InequalitySexual and Reproductive HealthFamily, Maternal & Child HealthMethodology

Immune correlates of HIV exposure without infection in foreskins of men from Rakai, Uganda

TitleImmune correlates of HIV exposure without infection in foreskins of men from Rakai, Uganda
Publication TypeJournal Article
Year of Publication2014
AuthorsProdger, JL, Hirbod, T, Kigozi, G, Nalugoda, F, Reynolds, SJ, Galiwango, R, Shahabi, K, Serwadda, D, Wawer, MJ, Gray, RH, Kaul, R
JournalMucosal Immunol
Date PublishedMay
ISBN Number1935-3456 (Electronic)1933-0219 (Linking)
Accession Number24150258
KeywordsSexual and Reproductive Health

Human immunodeficiency virus (HIV) susceptibility is heterogenous, with some HIV-exposed but seronegative (HESN) individuals remaining uninfected despite repeated exposure. Previous studies in the cervix have shown that reduced HIV susceptibility may be mediated by immune alterations in the genital mucosa. However, immune correlates of HIV exposure without infection have not been investigated in the foreskin. We collected sub-preputial swabs and foreskin tissue from HESN (n=20) and unexposed control (n=57) men undergoing elective circumcision. Blinded investigators assayed swabs for HIV-neutralizing IgA, innate antimicrobial peptides, and cytokine levels. Functional T-cell subsets from foreskin tissue were assessed by flow cytometry. HESN foreskins had elevated alpha-defensins (3,027 vs. 1,795 pg ml(-1), P=0.011) and HIV-neutralizing IgA (50.0 vs. 13.5% of men, P=0.019). Foreskin tissue from HESN men contained a higher density of CD3 T cells (151.9 vs. 69.9 cells mm(-2), P=0.018), but a lower proportion of these was Th17 cells (6.12 vs. 8.04% of CD4 T cells, P=0.007), and fewer produced tumor necrosis factor alpha (TNFalpha) (34.3 vs. 41.8% of CD4 T cells, P=0.037; 36.9 vs. 45.7% of CD8 T cells, P=0.004). A decrease in the relative abundance of susceptible CD4 T cells and local TNFalpha production, in combination with HIV-neutralizing IgA and alpha-defensins, may represent a protective immune milieu at a site of HIV exposure.