The NLRP3 inflammasome activation boosts lung injury, inflammation, and macrolide resistance in mycoplasma pneumoniae pneumonia.

The increase in the number of macrolide-resistant Mycoplasma pneumoniae (MP) poses a threat to human health worldwide. The present research investigates the role of the NLRP3 inflammasome in mycoplasma pneumoniae pneumonia (MPP). MPP patient (n = 40) and healthy control (n = 20)-derived serum samples were collected. MP (strain ATCC15531)-infected C57BL/6 J or Nlrp3-/- mice with or without MCC950 treatment were used to explore the role of the NLRP3 inflammasome. The concentrations of inflammatory cytokines were determined by enzyme-linked immunosorbent assay. Histomorphological changes were determined by hematoxylin-eosin staining. The transcriptional and translational levels of NLRP3 were detected with quantitative PCR and western blot. Serum interleukin (IL)-1β and IL-18 levels were higher in MPP patients, along with elevated NLRP3 mRNA and protein levels. High NLRP3 expression was associated with fever duration, duration of admission, c-reactive protein and lactate dehydrogenase levels, and macrolide resistance. During the progression of MP infection, the NLRP3 inflammasome was progressively activated in mice, accompanied by increasing lung injury and inflammation. However, MP-infected Nlrp3-/- mice showed decreased lung injury and inflammation. Additionally, MCC950 weakened lung injury and inflammation in MPP mice, and the combination of azithromycin and MCC950 exerted a stronger effect than azithromycin or MCC950 alone. The NLRP3 inflammasome activation boosts lung injury, inflammation, and macrolide resistance in MPP, implying that interfering with the NLRP3 inflammasome may be a stratagem for MPP administration.