The different chemokine profile in HIV-exposed seronegative persons

The studies on human population infected with or exposed to HIV have brought the description of several virus-refractory phenotypes. Among them are long-time non-progressors and HIV-exposed seronegative persons. The first group is able to control virus replication without the anti-retroviral therapy, maintain the normal CD4 T cell number and avoid the chronic immune activation that is normally associated with HIV infection. In consequence, long-time non-progressors can live with the presence of HIV for many years with minimal or without any ill effects. The second group is less widely known and comprises people who despite the persistent exposure to the virus do not become infected. In ordinary circumstances HIV gets into the body through mucosal surfaces at genital organs. HIV-exposed seronegative persons (HESN) appear to differ from the virus-sensitive population in terms of chemokine profile at the natural infection site.

The link: http://www.nature.com/mi/journal/v5/n3/abs/mi20127a.html

The study is conducted among Kenyan commercial sex workers divided into three categories. The experimental group includes HESN women, whereas control groups are HIV-1 negative women and HIV-1 infected patients. Authors analyze the cytokine/chemokine profile in the cervicovaginal lavage of each group. They detects that MIG and IP-10 (two IFN-γ inducible chemokines involved in the leukocyte trafficking) and cytokine IL-1α are expressed at lower level in the HESN cohort. Both chemokines are involved in the mucosal migration of activated CD4 T cells – the main HIV target. Hence one of HESN phenotype explanation might be that these people display the state of immune quiescence at their genital mucosa and simply do have enough number of activated CD4 T cells to become infected by virus.

To validate this point investigators examine plasma chemokine/cytokine profile in all studied groups as lymphocytes migrate to mucosal surfaces according to the chemokine gradient between blood and mucosa. They demonstrate that MIG levels in HESN group were higher in systemic compartments than at the genital mucosa whereas the HIV-1 negative population shows the opposite trend. Additionally, HESN subjects uniquely display the decreasing gradient for IP-10 from plasma to mucosal surfaces. The supportive data in this paper include the analysis of CXCR3 (the receptor bound by MIG and IP-10) on CD4 and CD8 T cells collected from the genital mucosa. Authors also study the expression of antiproteases in the genital tract as they are important factors regulating mucosal chemokine levels. It would be interesting to know what really drives the decreased chemokine levels in the genital tract of HESN.

J Lajoie, J Juno, A Burgener, S Rahman, K Mogk, C Wachihi, J Mwanjewe, F A Plummer, J Kimani, T B Ball, and K R Fowke (2012). A distinct cytokine and chemokine profile at the genital mucosa is associated with HIV-1 protection among HIV-exposed seronegative commercial sex workers Mucosal Immunology DOI: 10.1038/mi.2012.7

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