Protective role of macrophages from maternal–fetal interface in unvaccinated coronavirus disease 2019 pregnant women

Pregnant women represent a high‐risk population for Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) infection. The presence of SARS‐CoV‐2 has been reported in placenta from infected pregnant women, but whether the virus influences placenta immune response remains unclear. We investigated the properties of maternal–fetal interface macrophages (MFMs) in a cohort of unvaccinated women who contracted coronavirus disease 2019 (COVID‐19) during their pregnancy. We reported an infiltration of CD163 + macrophages in placenta from COVID‐19 women 19 whereas lymphoid compartment was not affected. Isolated MFMs exhibited nonpolarized activated signature ( NOS 2, IDO1 , IFNG , TNF , TGFB ) mainly in women infected during the second trimester of pregnancy. COVID‐19 during pregnancy primed MFM to produce type I and III interferon response to SARS‐CoV‐2 (Wuhan and δ strains), that were unable to elicit this in MFMs from healthy pregnant women. COVID‐19 also primed SARS‐CoV‐2 internalization by MFM in an angiotensin‐converting enzyme 2‐dependent manner. Activation and recall responses of MFMs were influenced by fetal sex. Collectively, these findings support a role for MFMs in the local immune response to SARS‐CoV‐2 infection, provide a basis for protective placental immunity in COVID‐19, and highlight the interest of vaccination in pregnant women.