Community-acquired respiratory distress syndrome (CARDS) toxin is a key driver of Mycoplasma pneumoniae–mediated disease, yet its pathogenic mechanisms remain incompletely understood. Here, we established female C57BL/6J murine pneumonia models by intratracheal injection of CARDS toxin (700 pmol per mouse). In wild-type mice (n = 3 per group), single-cell and bulk RNA sequencing were performed to characterize functional alterations of lung macrophages. Pulmonary inflammation was evaluated by immunostaining and PCR analyses in wild-type (n = 3), Lyz2-Mmp12^−/− (n = 4), and Mmp12-CreERT2×Rosa26-iDTR mice (n = 5). To interrogate downstream signaling, interleukin-17A (IL-17A) signaling was blocked using a neutralizing antibody. Clinical relevance was assessed using proteomic analysis and ELISA measurements of bronchoalveolar lavage fluid (BALF) proteins from disease control (n = 26) and M. pneumoniae pneumonia (MPP, n = 58) patients. We demonstrate that CARDS toxin exposure markedly increases the abundance of Mmp12^high macrophages in the murine lung, accompanied by overactivation of pro-inflammatory cytokine signaling. Macrophage-specific Mmp12 knockout attenuated CARDS toxin-induced pulmonary inflammation. Mechanistically, MMP12 promoted T helper 17 cells activation and subsequent IL-17A secretion via SPP1 and FN1, thereby exacerbating pulmonary inflammation. Notably, IL-17A blockade significantly mitigated these responses. Furthermore, MMP12 and IL-17A levels were elevated in the BALF of MPP patients. Collectively, these findings define a pro-inflammatory MMP12–IL-17A axis mediating CARDS toxin-driven pulmonary pathology, highlighting promising therapeutic targets for managing M. pneumoniae–associated respiratory disease.

At the BIOHK2024, held on September 11–14, 2024, the roundtable discussion titled “Time is now: Preparing for the next pandemic,” brought together Professors Jun Liu, George Fu Gao, Kwok-Yung Yuen, Lit Man Leo Poon, and Nan Song. They explored the current state of global readiness for impending viral threats, focusing on the necessity for enhanced surveillance, improved diagnostic technologies, and the development of more efficient vaccines and drugs. The panel underscored the importance of a coordinated global response, the role of vaccination in mitigating pandemic impacts, and the challenges posed by emerging viruses and their variants. They also highlighted the potential of artificial intelligence in disease prediction and basic researches, and also the need for continuous investment in pandemic preparedness to address the gaps exposed by the coronavirus disease 2019 (COVID-19) pandemic. The discussion concluded on a note of cautious optimism, emphasizing the importance of learning from past experiences and the resilience demonstrated by many countries during the recent pandemic.