A distinct cytokine and chemokine profile at the genital mucosa is associated with HIV-1 protection among HIV-exposed seronegative commercial sex workers.
The predominance of HIV-1 sexual transmission requires a greater understanding of the interaction between HIV-1 and the mucosal immune system. The study of HIV-1-exposed seronegative (HESN) individuals serves as a model to identify the correlates of protection and to aid in microbicide development. A total of 22 cytokines/chemokines were analyzed at the systemic and mucosal compartments in 57 HESN, 51 HIV-1-negative, and 67 HIV-1-infected commercial sex workers from Nairobi, Kenya. HESN individuals had significantly lower expression of monokine induced by interferon-γ (MIG), interferon-γ-induced protein 10 (IP-10), and interleukin-1α (IL-1α) in their genital mucosa compared with controls. HESN cytokine expression also distinctly correlates with mucosal antiproteases, suggesting that HESN individuals have a unique pattern of mucosal chemokine/cytokine expression, which may result in reduced trafficking at the mucosa. These data support the immune quiescence model of protection, whereby lower T-cell activation/recruitment at the mucosal compartment reduces HIV-1 target cell numbers and is an important component of natural protection from HIV-1.
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
J
J
Lajoie
J
J
Juno
A
A
Burgener
S
S
Rahman
K
K
Mogk
C
C
Wachihi
J
J
Mwanjewe
F A
FA
Plummer
J
J
Kimani
T B
TB
Ball
K R
KR
Fowke
D000328:Adult; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005835:Genitalia / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology*; D018023:HIV Seronegativity; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D007630:Kenya; D008875:Middle Aged; D060386:Sex Workers
C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C508584:IL1A protein, human; D053582:Interleukin-1alpha