Low Immune Activation in the Ectocervix of HIV-Exposed Seronegative Commercial Sex Workers

Anna Gibbs1, Taha Hirbod1, Terry B Ball2, Rupert Kaul3, Joshua Kimani4, Annelie Tjernlund1, Kristina Broliden1
Affiliates: 1Karolinska Institutet, Stockholm, Sweden, 2University of Manitoba, Winnipeg, Canada, 3University of Toronto, Toronto, Canada, 4University of Nairobi, Nairobi, Kenya

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Background
Heterogeneity in susceptibility to HIV infection has been demonstrated in HIV-exposed seronegative (HESN) individuals and resistance against infection may partly be attributed to a low mucosal immune activation state.

Methods
Cervical tissue samples were collected from HESN female sex workers (FSW) and HIV seropositive FSW (HIV+FSW) from the Pumwani cohort of FSW, Nairobi, Kenya. HIV seronegative lower risk women (HIV- LR) from the same geographical region were also included as controls. Protein and mRNA expression of selected immune markers were assessed by immunohistochemistry and qPCR, respectively, and compared between the study groups.

Results
The numbers of CD3+, CD8+, HLA-DR+, CCR5+ and MR+ cells in the ectocervix were comparable between the HESN FSW and HIV- LR study groups, however significantly higher in the HIV+ FSW group as compared to HESN FSW. Furthermore, there was no difference in the mRNA expression of the pro-inflammatory cytokines (IFN-gamma, TNF, IL-6, IL-17 and IL-22) between the HESN FSW and HIV- LR groups, although the mRNA levels of these cytokines were significantly higher in the HIV+ FSW group as compared to HESN FSW. In addition, the HESN FSW group had both significantly lower CD4 mRNA expression and CD4 protein expression as compared to the other two study groups.

Conclusions
Despite active commercial sex work these relatively resistant HESN FSW had a low immune activation state as assessed in ectocervical tissue samples. They also had relatively low numbers of HIV target cells (CD4+ cells). This mucosal immune phenotype may be beneficial in the resistance against HIV infection.