Schistosoma mansoni Infection in Ugandan Men Is Associated with Increased Abundance and Function of HIV Target Cells in Blood, but Not the Foreskin: A Cross-sectional Study.
BACKGROUND
Schistosoma mansoni infection has been associated with an increased HIV prevalence in humans and SHIV incidence in primate models. We hypothesized that immune activation from this gastrointestinal mucosa infection would increase highly HIV-susceptible CD4 T cell subsets in the blood and the foreskin through common mucosal homing.


RESULTS
Foreskin tissue and blood were obtained from 34 HIV- and malaria-uninfected Ugandan men who volunteered for elective circumcision, 12 of whom were definitively positive for S. mansoni eggs in stool and 12 definitively negative for both S. mansoni eggs and worm antigen. Tissue and blood T cell subsets were characterized by flow cytometry and immunohistochemistry (IHC). Th17 and Th1 cells from both the blood and foreskin expressed higher levels of CCR5 and were more activated than other CD4 T cell subsets. S. mansoni-infected men had a higher frequency of systemic Th1 cells (22.9 vs. 16.5% of blood CD4 T cells, p<0.05), Th17 cells (2.3 vs. 1.5%, p<0.05), and Th22 cells (0.5 vs. 0.3%, p<0.01) than uninfected men. Additionally, Th17 cells in the blood of S. mansoni-infected men demonstrated enhanced function (28.1 vs. 16.3% producing multiple cytokines, p = 0.046). However, these immune alterations were not observed in foreskin tissue.


CONCLUSIONS
S. mansoni infection was associated with an increased frequency of highly HIV-susceptible Th1, Th17 and Th22 cell subsets in the blood, but these T cell immune differences did not extend to the foreskin. S. mansoni induced changes in T cell immunology mediated through the common mucosal immune system are not likely to increase HIV susceptibility in the foreskin.
Departments of Medicine and Immunology, University of Toronto, Toronto, Canada.
Jessica L
JL
Prodger
Uganda Virus Research Institute-International AIDS Vaccine Initiative HIV Vaccine Program, Entebbe, Uganda.
Aloysious
A
Ssemaganda
Uganda Virus Research Institute-International AIDS Vaccine Initiative HIV Vaccine Program, Entebbe, Uganda.
Ali
A
Ssetaala
Uganda Virus Research Institute-International AIDS Vaccine Initiative HIV Vaccine Program, Entebbe, Uganda.
Paul K
PK
Kitandwe
Uganda Virus Research Institute-International AIDS Vaccine Initiative HIV Vaccine Program, Entebbe, Uganda.
Enoch
E
Muyanja
Uganda Virus Research Institute-International AIDS Vaccine Initiative HIV Vaccine Program, Entebbe, Uganda.
Juliet
J
Mpendo
Uganda Virus Research Institute-International AIDS Vaccine Initiative HIV Vaccine Program, Entebbe, Uganda.
Annet
A
Nanvubya
Uganda Virus Research Institute-International AIDS Vaccine Initiative HIV Vaccine Program, Entebbe, Uganda.
Mathias
M
Wambuzi
Uganda Virus Research Institute-International AIDS Vaccine Initiative HIV Vaccine Program, Entebbe, Uganda; International AIDS Vaccine Initiative, New York, New York, United States of America.
Leslie
L
Nielsen
Uganda Virus Research Institute-International AIDS Vaccine Initiative HIV Vaccine Program, Entebbe, Uganda; School of Public Health, College of Health Sciences, Makerere University, Kampala, Uganda.
Noah
N
Kiwanuka
Departments of Medicine and Immunology, University of Toronto, Toronto, Canada.
Rupert
R
Kaul
D000293:Adolescent; D000328:Adult; D000818:Animals; D001769:Blood / Q000276:immunology*; D003430:Cross-Sectional Studies; D004198:Disease Susceptibility; D005434:Flow Cytometry; D052816:Foreskin / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014454:Uganda; D055815:Young Adult