AUTHOR=Palani Sunil , Uddin Md Bashir , McKelvey Michael , Shao Shengjun , Sun Keer 

TITLE=Immune predisposition drives susceptibility to pneumococcal pneumonia after mild influenza A virus infection in mice

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1272920

DOI=10.3389/fimmu.2023.1272920

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>A frequent sequela of influenza A virus (IAV) infection is secondary bacterial pneumonia. Therefore, it is clinically important to understand the genetic predisposition to IAV and bacterial coinfection.</p></sec><sec><title>Methods</title><p>BALB/c and C57BL/6 (B6) mice were infected with high or low-pathogenic IAV and <italic>Streptococcus pneumoniae</italic> (<italic>SPn</italic>). The contribution of cellular and molecular immune factors to the resistance/susceptibility of BALB/c and B6 mice were dissected in nonlethal and lethal IAV/<italic>SPn</italic> coinfection models.</p></sec><sec><title>Results</title><p>Low-virulent IAV X31 (H3N2) rendered B6 mice extremely susceptible to SPn superinfection, while BALB/c mice remained unaffected. X31 infection alone barely induces IFN-γresponse in two strains of mice; however, SPn superinfection significantly enhances IFN-γ production in the susceptible B6 mice. As a result, IFN-γ signaling inhibits neutrophil recruitment and bacterial clearance, leading to lethal X31/<italic>SPn</italic> coinfection in B6 mice. Conversely, the diminished IFN-γ and competent neutrophil responses enable BALB/c mice highly resistant to X31/SPn coinfection.</p></sec><sec><title>Discussion</title><p>The results establish that type 1 immune predisposition plays a key role in lethal susceptibility of B6 mice to pneumococcal pneumonia after mild IAV infection.</p></sec>