TNF superfamily member 14 drives post-influenza depletion of alveolar macrophages, enabling secondary pneumococcal pneumonia.

ABSTRACT: Secondary bacterial infection, often caused by Streptococcus pneumoniae, is one of the most frequent and severe complications of influenza A virus-induced (IAV-induced) pneumonia. Phenotyping of the pulmonary immune cell landscape after IAV infection revealed a substantial depletion of the tissue-resident alveolar macrophage (TR-AM) population at day 7, which was associated with increased susceptibility to S. pneumoniae outgrowth. To elucidate the molecular mechanisms underlying TR-AM depletion, and to define putative targets for treatment, we combined single-cell transcriptomics and cell-specific PCR profiling in an unbiased manner, using in vivo models of IAV infection and IAV and S. pneumoniae coinfection. The TNF superfamily 14 (TNFSF14) ligand/receptor axis was revealed as the driving

SUBMITTER: Malainou C 

PROVIDER: S-EPMC12807475 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature