Influenza Infection Induces Alveolar Macrophage Dysfunction and Thereby Enables Noninvasive Streptococcus pneumoniae to Cause Deadly Pneumonia.

In this study, we revisited these controversies over key pathogenic mechanisms in a lethal model of secondary bacterial pneumonia with an S. pneumoniae strain that is innocuous to mice in the absence of influenza infection. Using a series of in vivo models, we demonstrate that rather than a systemic suppression of immune responses or neutrophil function, influenza infection activates IFN-γR signaling and abrogates AM-dependent bacteria clearance and thereby causes extreme susceptibility to pneumococcal infection. Importantly, using mice carrying conditional knockout of Ifngr1 gene in different myeloid cell subsets, we demonstrate that influenza-induced IFN-γR signaling in AMs impairs their antibacterial function, thereby enabling otherwise noninvasive S. pneumoniae to cause deadly pneumonia. PMID: 32796026 [PubMed - as supplied by publisher]
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research