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

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-gamma response in two strains of mice; however, SPn superinfection significantly enhances IFN-gamma production in the susceptible B6 mice. As a result, IFN-gamma signaling inhibits neutrophil recruitment and bacterial clearance, leading to lethal X31/SPn coinfection in B6 mice. Conversely, the diminished IFN-gamma 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.

Automated summary

The susceptibility of B6 mice to pneumococcal pneumonia after mild IAV infection is primarily attributed to the type 1 immune predisposition. IFN-γ signaling inhibits neutrophil recruitment and bacterial clearance in B6 mice, leading to lethal coinfection.