| First Author | Palani S | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1272920 | PubMed ID | 37771584 |
| Mgi Jnum | J:347990 | Mgi Id | MGI:7537830 |
| Doi | 10.3389/fimmu.2023.1272920 | Citation | Palani S, et al. (2023) Immune predisposition drives susceptibility to pneumococcal pneumonia after mild influenza A virus infection in mice. Front Immunol 14:1272920 |
| abstractText | 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-gammaresponse 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. |
