Publication date: Oct 16, 2024

How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages. We identify a group of monocyte-derived Slamf9 macrophages, which are induced after SARS-CoV-2 infection and resistant to impairment caused by SARS-CoV-2. Slamf9 macrophages contain SARS-CoV-2, recruit and interact with Isg12Cst7 neutrophils to clear the viruses. After viral clearance, Slamf9 macrophages differentiate into Trem2 and Fbp1 macrophages, contributing to inflammation resolution at the late stage, and finally replenish alveolar macrophages. These findings are validated in a SARS-CoV-2-infected hACE2 mouse model and confirmed with publicly available human autopsy single-cell RNA-seq data, demonstrating the potential role of Slamf9 macrophages and their coordination with neutrophils in post-injury tissue repair and inflammation resolution.

Semantics

Original Article