TLR7 alters the maternal immune landscape during influenza A infection to increase maternal and fetal morbidity.

Abstract

Pregnant women infected with influenza A virus (IAV) are at increased risk of severe disease, leading to maternal and fetal complications. Toll-like receptor 7 (TLR7) recognizes single-stranded RNA viruses, including IAV, yet its role in maternal immune responses and pregnancy outcomes during IAV infection is poorly understood. Here, we demonstrate that TLR7-knockout (TLR7^-/-) pregnant mice showed reduced disease severity, despite similar pulmonary viral titers to wild-type (WT) mice. TLR7^-/- dams exhibited distinct pulmonary responses, including reduced lymphocyte infiltration, enhanced neutrophil response, and a shift from type I to type II interferon activity. TLR7 signaling was found to be essential for the development of IAV-induced vascular dysfunction during pregnancy. Offspring from TLR7^-/- mice showed improved body weight and reduced placental and fetal brain inflammation compared to WT counterparts. We provide evidence that TLR7 is a critical mediator of adverse pregnancy outcomes during IAV infection and a potential therapeutic target to reduce maternal and fetal morbidity.