Acute response to pathogens in the early human placenta at single-cell resolution

The placenta is a selective maternal-fetal barrier that provides nourishment and protection from infections. However, certain pathogens can attach to and even cross the placenta, causing pregnancy complications with potential lifelong impacts on the child’s health. Here, we profiled at the single-cell level the placental responses to three pathogens associated with intrauterine complications—Plasmodium falciparum, Listeria monocytogenes, and Toxoplasma gondii. We found that upon exposure to the pathogens, all placental lineages trigger inflammatory responses that may compromise placental function. Additionally, we characterized the responses of fetal macrophages known as Hofbauer cells (HBCs) to each pathogen and propose that they are the probable niche for T. gondii. Finally, we revealed how P. falciparum adapts to the placental microenvironment by modulating protein export into the host erythrocyte and nutrient uptake pathways. Altogether, we have defined the cellular networks and signaling pathways mediating acute placental inflammatory responses that could contribute to pregnancy complications. [Display omitted] •Single-cell census of early placental human explants exposed to congenital pathogens•Infections trigger a general inflammatory response across all placental lineages•Hofbauer cells elicit pathogen-specific responses and demonstrate antimicrobial abilities•Plasmodium adapts to the placenta through erythrocyte remodeling and nutrient uptake Placental infections during early pregnancy can lead to pregnancy complications and developmental anomalies. Hoo, Ruiz-Morales, Kelava et al. profiled the placenta at the single-cell level upon exposure to Listeria, Plasmodium, and Toxoplasma. They uncovered general inflammation and unique Hofbauer cell responses. Additionally, they revealed Plasmodium adaptation to the placental microenvironment.