PD02.03
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. The thickness of the ectocervical epithelium was analysed on sequential tissue sections.
Results: The mRNA levels of the cell makers CD3, CCR5, HLA-DR, DC-SIGN, Langerin, CD69 and of the pro-inflammatory cytokine markers IFN-alpha, IFN-gamma, TNF-alpha, IL-6, IL-17 and IL-22 were comparable between the HESN FSW and the HIV- LR study groups. Most of these markers were however significantly lower in the HESN FSW study group as compared to the HIV+FSW study group. Furthermore, the HESN FSW group had significantly lower mRNA expression as well as protein expression of CD4+ cells as compared to the other two groups and they had significantly more mRNA and protein expression of CD8 as compared to the HIV- LR group. The ectocervical epithelium of the HESN FSW samples was generally thicker than that of 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) and a thicker epithelium than the control groups. This mucosal immune phenotype may be beneficial in the resistance against HIV infection.