Suppressing neutrophil itaconate production attenuates Mycoplasma pneumoniae pneumonia

• DOI: 10.1371/journal.ppat.1012614
• Publication Date: 2024-11-05T18:34:18Z
• Authors: Cui Wang; Jun Wen; Zijun Yan; Yujun Zhou; Zhande Gong; Ying Luo; Zhenkui Li; Kang Zheng; Haijun Zhang; Nan Ding; Chuan Wang; Cuiming Zhu; Yimou Wu; Aihua Lei
• Keywords: QH301-705.5; Immunologic diseases. Allergy; RC581-607; Biology (General); Research Article

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in which neutrophils play critical role. Immune-responsive gene 1 (IRG1), responsible for itaconate production, has emerged as an important regulator inflammation and infection, but its role during M . infection remains unknown. Here, we reveal that endogenous pro-inflammatory metabolite infection. Irg1 knockout (KO) mice had lower levels bacterial burden, lactate dehydrogenase (LDH), cytokines compared with wild-type (WT) controls after Neutrophils were the major cells producing mice. Neutrophil counts positively correlated concentrations bronchoalveolar lavage fluid (BALF) patients severe pneumonia. Adoptive transfer KO neutrophils, or administration β-glucan (an inhibitor expression), significantly attenuated Mechanistically, impaired neutrophil killing suppressed apoptosis via inhibiting mitochondrial ROS. Moreover, induced expression by activating NF-κB STAT1 pathways involving TLR2. Our data thus identify /itaconate pathway potential therapeutic target treatment