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39414783
Single-cell spatiotemporal analysis of the lungs reveals Slamf9+ macrophages involved in viral clearance and inflammation resolution.

Cell Discov, 2024/10/16;10(1):104.

Cong B[1, 2], Dong X[3], Yang Z[2], Yu P[4], Chai Y[2], Liu J[2], Zhang M[1], Zang Y[3], Kang J[3], Feng Y[3], Liu Y[3], Feng W[3], Wang D[5], Deng W[4], Li F[4], Song Z[4], Wang Z[2], Chen X[1], Qin H[1], Yu Q[6], Li Z[7, 8], Liu S[7, 8], Xu X[3], Zhong N[8], Ren X[9], Qin C[10], Liu L[11], Wang J[12], Cao X[13, 14]

Affiliations

PMID: 39414783DOI: 10.1038/s41421-024-00734-4

Abstract
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 Isg12+Cst7+ 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.
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