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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Immune correlates of HIV exposure without infection in foreskins of men from Rakai, Uganda
Mucosal Immunology, Volume 7, No. 3, Year 2014
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Description
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 susceptibilitymay bemediated by immune alterations in the genitalmucosa.However, immune correlates ofHIVexposure without infection have not been investigated in the foreskin. We collected sub-preputial swabs and foreskin tissue from HESN (n1/420) and unexposed control (n1/457) men undergoing elective circumcision. Blinded investigators assayed swabs for HIV-neutralizing IgA, innate antimicrobial peptides, and cytokine levels. Functional T-cell subsets fromforeskin tissuewere assessed by flowcytometry.HESNforeskins had elevated a-defensins (3,027 vs. 1,795 pgml1,P1/40.011) and HIV-neutralizing IgA(50.0 vs. 13.5%ofmen,P1/40.019).Foreskin tissue fromHESNmen contained a higherdensityofCD3 T cells (151.9 vs. 69.9 cellsmm2, P1/40.018), but a lower proportion of these was Th17 cells (6.12 vs. 8.04%of CD4 Tcells, P1/40.007), and fewer produced tumor necrosis factor a (TNFa) (34.3 vs. 41.8% of CD4 Tcells, P1/40.037; 36.9 vs. 45.7%of CD8 T cells, P1/40.004). A decrease in the relative abundance of susceptible CD4 T cells and local TNFa production, in combinationwithHIV-neutralizing IgAand a-defensins,may represent a protective immunemilieu at a site ofHIVexposure. © 2014 Society for Mucosal Immunology.
Authors & Co-Authors
Prodger, Jessica L.
Canada, Toronto
University of Toronto
Hirbod, Taha
Sweden, Stockholm
Karolinska Institutet
Kigozi, Godfrey G.
Uganda, Kalisizo
Rakai Health Sciences Program
Nalugoda, Fred Kakaire
Uganda, Kalisizo
Rakai Health Sciences Program
Reynolds, Steven James
Uganda, Kalisizo
Rakai Health Sciences Program
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
United States, Baltimore
Johns Hopkins School of Medicine
Galiwango, Ronald Moses
Uganda, Kalisizo
Rakai Health Sciences Program
Shahabi, Kamnoosh
Canada, Toronto
University of Toronto
Serwadda, David Musoke
Uganda, Kalisizo
Rakai Health Sciences Program
Uganda, Kampala
Makerere University School of Public Health
Wawer, Maria J.
Uganda, Kalisizo
Rakai Health Sciences Program
United States, Baltimore
Johns Hopkins Bloomberg School of Public Health
Gray, Ronald H.
Uganda, Kalisizo
Rakai Health Sciences Program
United States, Baltimore
Johns Hopkins Bloomberg School of Public Health
Kaul, Rupert
Canada, Toronto
University of Toronto
Statistics
Citations: 43
Authors: 11
Affiliations: 7
Identifiers
Doi:
10.1038/mi.2013.83
ISSN:
19330219
e-ISSN:
19353456
Research Areas
Cancer
Infectious Diseases
Study Locations
Uganda
Participants Gender
Male