Yanan Wu, Qi Zhu, Jing Liu, Hongyun Chuan, Lingyu He, Mingqing Wang, Lilan Xu, R Z Zhang, Yao Liu, Guoyang Liao, Weidong Li, Chengquan Sun, Jian Zhou
Coinfection with influenza virus and Mycoplasma pneumoniae (MP) increases mortality during influenza pandemics; however, its specific impact on Mycoplasma Pneumoniae Pneumonia (MPP) patients or animal models remains unclear. The underlying mechanisms of influenza A virus (IAV)–MP interactions are not fully understood. To investigate the causes of heightened mortality, we established a lethal sequential coinfection mouse model using H3N2 influenza and MP. Coinfection led to prolonged viral persistence, enhanced pulmonary immune cell infiltration, and significantly elevated levels of inflammatory cytokines (IL-6, CCL3, CCL4, and G-CSF; p < 0.05–0.001), culminating in severe pneumonia. Notably, coinfected mice exhibited impaired CD8+ T-cell responses (p < 0.05) and increased pulmonary IL-6 and IL-1α levels (p < 0.05) compared with the controls. Our findings demonstrate that IAV-MP coinfection induces immune-mediated lung injury, which likely contributes to the observed mortality. This study provides critical insights into the immunopathogenesis of coinfection and suggests potential therapeutic targets for managing coinfected patients.