Unique expression of genes influencing transendothelial leukocyte migration in HIV-1 resistant women in the pumwani sex worker cohort.

Abstract

Objective: The Pumwani Sexworker Cohort in Nairobi, Kenya has enrolled >2100 women from 1985 to 2002. A small subset of women enrolled during this period remain HIV uninfected despite high-risk sex work exposures. This study investigated the expression of genes involved in leukocyte movement and migration and their role in HIV resistance.

Methods: Whole blood was collected from 75 HIV uninfected women: 38 HIV resistant women (average of 15.39 negative years) and 37 susceptible new enrollees (average of 1.027 negative years). The mRNA expression of 84 genes was analyzed using a custom RT2 Profiler PCR-array and compared between HIV resistant women and HIV negative susceptible controls. The function and influence of genes with mRNA significantly differentially expressed were analyzed using Ingenuity Pathway Analysis (QIAGEN) and Pathway Studio (Elsevier).

Results: Eighteen genes were significantly up-expressed in HIV resistant women. Among them, 16 genes are involved in the leukocyte movement and migration (p < 0.00001). Among them, 4 genes (CTNNB1, ITGB1, PIK3CA and PTPN11) are involved in transendothelial leukocyte migration signaling (p < 0.00001), 8 genes (CTNNB1, DPP4, ITGB1, PIK3CA, PTPN11, TICAM1, TIMP1, VCAN) are involved in cellular infiltration by leukocytes (p < 0.00001), and 6 genes (CTNNB1, ITGB1, MAP3K4, PIK3CA, PTPN11, TIMP1) are involved in the Leukocyte Extravasation Signaling (p < 0.00001).

Discussion/conclusions: We propose that the HIV resistant women of the PSC may exhibit a unique leukocyte migratory response in dealing with pathogen infection. The potential mechanisms could contribute to the unique leukocyte migratory response: modifications to the PI3K/AKT signaling, extracellular matrix remodeling, integrin structure and function, and activation of T-cell receptors.