Cervicovaginal cells from HIV-infected South African women express higher levels of genes involved in microbial pattern recognition and inflammatory pathways than peripheral blood mononuclear cells
Andrea Gillian Abrahams1*, Arghavan Alisoltanidehkordi1, Jason Skinner3, Damien Chaussabel3,4, Jo-Ann S. Passmore1,2,6, Lindi Masson1,2*
1Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, South Africa; 2Centre for the AIDS Programme of Research in South Africa (CAPRISA), South Africa; 3Baylor Institute for Immunology Research, Texas, USA; 4Sidra Medicine, Qatar; 6National Health Laboratory Services, South Africa.
The interplay between the female genital tract (FGT) microbiome and immune system is critical for defence against pathogens, while maintaining tolerance to commensal bacteria and allogenic semen. However, FGT inflammation increases risk of HIV acquisition, mother-to-child transmission and transmission to partners. Using transcriptomics, we compared the expression of genes involved in inflammatory signalling pathways between cervical mononucleocytes (CMC) and blood mononucleocytes (PBMC) from HIV-infected women.
Cervical cytobrushes and blood were collected from HIV-infected South African women on antiretroviral therapy (ART), cells were isolated and mRNA was extracted. Clinical signs and symptoms of genital infections were recorded at the time of sampling. Gene expression was evaluated in CMCs [RNA Integrity Number (RIN): 5.3-8.4] and matching PBMCs (RIN: 8.6-9.8) using Illumina HumanHT-12 v3 Expression BeadChip. Data analysis was performed using R studio and DAVID NIH.
A total of 205 genes were differentially expressed between CMCs and PBMCs, with 136 genes upregulated (logFC≥1.5) and 69 genes downregulated (logFC≤-1.5). Although none of the women had clinical signs of a genital infection, genes involved in inflammatory signalling pathways, Nuclear Factor-kappa B, Tumor necrosis factor, Toll-like receptor and NOD-like receptor signalling were significantly upregulated in CMCs compared to PBMCs (adjusted p=0.002, p=0.026, p=0.026, p=0.044, respectively). Key genes in these pathways were IL-1β, NFkBI and IL-8 (p=0.008, p=0.010, p=0.014, respectively).
In conclusion, we found that genes involved in inflammatory signalling pathways were upregulated in the FGT compared to blood of HIV-infected women, that may influence HIV shedding and transmission.