An immune program in early embryogenesis: our first microbial encounter in 4D

During early development, internal cues guide embryonic cells to acquire fate and perform morphogenesis. In nature, embryos develop within particular microenvironments, whose precise roles in regulating embryogenesis remain largely unexplored. In this study, we focus on the microbiological environment that early embryos may encounter, such as the bacteria that can prevalently infect the human uterus. Using zebrafish and mouse models of bacterial infection in early embryos, we show that epithelial cells of the embryonic surface can detect, ingest, and destroy bacteria by activating a distinct immune gene program essential for normal development. Our multi-scale analysis further reveals the cytoskeletal machinery mediating protrusion dynamics for bacterial engulfment. Remarkably, we demonstrate similar phagocytic abilities for clearing bacteria in human embryos. These findings have important implications for understanding the onset of innate immunity and the causes of human developmental failures, which underscore the role of the microenvironment in natural embryogenesis.