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

Front Immunol. 2023 Sep 13:14:1272920. doi: 10.3389/fimmu.2023.1272920. eCollection 2023.

Abstract

Introduction: 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.

Methods: BALB/c and C57BL/6 (B6) mice were infected with high or low-pathogenic IAV and Streptococcus pneumoniae (SPn). 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/SPn coinfection models.

Results: 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/SPn coinfection in B6 mice. Conversely, the diminished IFN-γ and competent neutrophil responses enable BALB/c mice highly resistant to X31/SPn coinfection.

Discussion: 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.

Keywords: Streptococcus pneumoniae; coinfection; genetic predisposition; influenza; pneumonia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Coinfection*
  • Humans
  • Influenza A Virus, H3N2 Subtype
  • Influenza A virus*
  • Influenza, Human*
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections*
  • Pneumonia, Pneumococcal*
  • Streptococcus pneumoniae
  • Superinfection*