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

Frontiers in Immunology

Immunology

Michael McKelvey¹  Keer Sun²  Sunil Palani²  Shengjun Shao²  Md Bashir Uddin² 

[1] Department of Experimental Pathology, University of Texas Medical Branch, Galveston, TX, United States;Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United States;

关键词: influenza;    Streptococcus pneumoniae;    coinfection;    genetic predisposition;    pneumonia;   

DOI  :  10.3389/fimmu.2023.1272920

 received in 2023-08-04, accepted in 2023-08-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionA 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.MethodsBALB/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.ResultsLow-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.DiscussionThe results establish that type 1 immune predisposition plays a key role in lethal susceptibility of B6 mice to pneumococcal pneumonia after mild IAV infection.

【 授权许可】

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Copyright © 2023 Palani, Uddin, McKelvey, Shao and Sun