Preterm birth in Zambian women is correlated with M1- pro-inflammatory macrophage polarization driven by HIV and anaerobic vaginal microbiota 2629

Abstract Description The goal of the Zambian Preterm Birth Prevention Study (ZAPPS) is to discover biological factors contributing to preterm birth (PTB). HIV infection and vaginal anaerobic bacteria are related to promoting inflammation and increased risk of PTB. Macrophages (CD14+CD68+) regulate immunity during pregnancy. M2 macrophages promote tolerance at the maternal-fetal interface during fetal development. M1 macrophages promote inflammation in response to pathogens and during labor. We hypothesize that preconception HIV exposed women will develop an exacerbated dominant M1 proinflammatory environment during the fetal development stage of pregnancy that, combined with the more anaerobe vaginal microbiota, will increase the risk of preterm birth. PBMCs, from a healthy African American female donor, were treated in vitro with longitudinally collected vaginal swab eluates (2nd and 3rd trimesters) from Zambian women with or without HIV who had term birth (TB) or spontaneous PTB (sPTB). Flow Cytometry was used to determine the percentage of M1 (IL1β+ and/or TNFα+) and M2 (TGFβ+ and/or IL10+) macrophages. We compared the ratio of M1 to M2 based on cytokine expression within each clinical group and control groups (M0, M1, M2). There is a correlation between a higher frequency of inflammatory M1 macrophages to immunotolerant M2 macrophages for women with sPTB when compared to women with TB- driven by a higher ratio of IL1β:IL10. Vaginal swabs could be used for early risk assessment of sPTB. Funding Sources Supported by NIH/NIAID 5P30AI050410-27, NIH/NICHD 5T32HD075731-09, The Bill and Melinda Gates Foundation, and UNC Chapel Hill. Topic Categories Mucosal and Regional Immunology (MUC)