Aggravated MRSA pneumonia secondary to influenza A virus infection is derived from decreased expression of IL‐1β

Shi, Yunfeng; Shi, Xiaohan; Liang, Jingjing; Luo, Jinmei; Ba, Junhui; Chen, Jianning; Wu, Benquan

Secondary methicillin‐resistant Staphylococcus aureus (MRSA) infection is a cause of severe pneumonia with high mortality during influenza A virus (IAV) pandemics. Alveolar macrophages (AMs) mount cellular defenses against IAV and MRSA infection, which occurs via the nucleotide‐binding domain‐like receptor protein 3 (NLRP3) inflammasome. However, the activity and function of the NLRP3 inflammasome in MRSA pneumonia secondary to IAV infection remain unclear. To clarify this, we studied MRSA infection secondary to IAV both in vitro and in mouse model. The expression of the NLRP3 inflammasome was evaluated by quantitative reverse transcription polymerase chain reaction, immunofluorescence, Western blot, and enzyme‐linked immunosorbent assay. The lung pathology and the rate of weight change were observed. We found that IAV infection for 1 week activated NLRP3 inflammasome. The enhanced expression of NLRP3, caspase‐1, and cleaved caspase‐1 was associated with MRSA infection secondary to IAV, but the expression of interleukin (IL)‐1β decreased in superinfection with MRSA both in vitro and in vivo. The aggravated inflammatory pathology in MRSA pneumonia secondary to IAV infection was associated with decreased expression of IL‐1β. And increased weight loss in MRSA pneumonia secondary to IAV infection was related to decreased concentration of IL‐1β in serum. It infers that superinfection with MRSA reduces expression of IL‐1β someway, and decreased expression of IL‐1β impairs the host immunity and leads to aggravated pneumonia. These results contributed to our understanding of the detailed activity of the NLRP3 inflammasome, IL‐1β, and their relationship with aggravation of MRSA pneumonia secondary to IAV infection. Immunotherapy targeting the IL‐1β signaling pathway could be possible therapeutic strategy for secondary MRSA pneumonia.