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

Area of Science:

• Reproductive Health
• Immunology
• Microbiome Research

Background:

• Preterm birth (<37 weeks gestation) affects 10% of infants globally, predominantly in low- and middle-income countries (LMICs).
• It is the leading cause of death for infants under 5 years old.
• Aberrant immune activation at the maternal-fetal interface is a common factor in adverse birth outcomes, including preterm birth, but its cause is unknown.

Purpose of the Study:

• To review how HIV and antiretroviral therapy alter macrophage function at the maternal-fetal interface.
• To examine the impact of vaginal microbiota changes on maternal-fetal immune responses.
• To propose a dual-hit model for preterm birth in sub-Saharan African women.

Main Methods:

• Literature review focusing on immune activation, HIV, vaginal microbiota, and preterm birth.
• Analysis of macrophage regulatory function in response to these factors.
• Development of a conceptual model linking these elements.

Main Results:

• Both HIV and specific vaginal commensals can promote inflammation and immune activation.
• Macrophage function at the maternal-fetal interface is potentially altered by HIV, therapy, and microbiota.
• A dual-hit model suggests macrophages mediate inflammation due to vaginal commensals and HIV.

Conclusions:

• HIV and vaginal microbiota dysbiosis are significant risk factors for preterm birth.
• Macrophages may act as key mediators in the inflammatory pathways leading to preterm birth.
• Understanding these interactions is crucial for developing diagnostics and interventions to improve maternal and infant health outcomes in LMICs.