Microbiota-dependent interferon-λ controls immunity of the uterus and maternal-fetal interface

Precise regulation of uterine immunity is required to support fundamental processes including reproduction and pathogen protection. How the local milieu and constitutive stressors, including the cervicovaginal microbiota, shape the delicate balance underlying uterine immunity is poorly understood. Here, we found that the cervicovaginal microbiota promotes both local immunity and the immunoregulatory activity of interferon lambdas (IFN-λ) in the uterus. Using murine models, we found a keystone role for IFN-λ in constraining the immune tone of this compartment, more specifically of innate lymphoid cells and Th17 cells. Conversely, in the context of pregnancy, IFN-λ promotes antibacterial responses at maternal-fetal barriers, and as a result controlling fetal and neonatal transmission. Collectively, this work demonstrates how IFN-λ integrates microbial signals under both steady state and pregnancy conditions thereby orchestrating key functions of the uterine immune system, namely immunoregulation and antibacterial protection.