Inflammation at the maternal-fetal interface: a perspective on interacting risk factors for preterm birth in sub-Saharan African women living with HIV

TL;DR

This paper explores how HIV and vaginal microbiota interact to cause inflammation, increasing preterm birth risk in sub-Saharan African women.

Contribution

The paper proposes a dual-hit model where macrophages mediate inflammation at the maternal-fetal interface due to HIV and microbiota changes.

Findings

HIV and vaginal microbiota changes both promote inflammation at the maternal-fetal interface.

Macrophages may act as mediators in preterm birth outcomes among HIV-positive women in sub-Saharan Africa.

A dual-hit model is proposed to explain interactions between HIV, microbiota, and immune activation.

Abstract

Globally, approximately 10% of all babies are born prematurely. The vast majority of preterm births, defined as birth <37 weeks of gestation, occur in low- and middle-income countries (LMICs) in Asia and Africa. Furthermore, premature birth has become the leading cause of death in infants under the age of 5 years. Thus, to improve maternal and infant health outcomes, better diagnostics and intervention strategies are urgently needed. However, the multifactorial etiology of preterm birth provides a major obstacle in achieving this goal. A common factor to many adverse birth outcomes, including preterm birth, is aberrant immune activation at the maternal-fetal interface. The specific cause of immune activation, however, remains unknown. Both HIV and an anaerobe-rich vaginal microbiota have been independently identified as risk factors for preterm birth, and both factors also promote inflammation and immune activation at mucosal sites. The interplay of HIV and microbiota is widely acknowledged, although mostly in the context of the intestinal microbiome. This review will highlight how the regulatory function of macrophages at the maternal-fetal interface can be altered in response to HIV and antiretroviral therapy and to changes in vaginal microbiota. We proceed to discuss interactions between the various factors and propose a dual-hit model in which macrophages act as mediators of inflammation at the maternal-fetal interface in response to specific vaginal commensals and HIV infection in sub-Saharan African women with preterm birth outcomes.

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