Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Sichuan Science-Observation Experimental Station of Veterinary Drugs and Veterinary Diagnostic Technique, Ministry of Agriculture and Rural Affairs, Chengdu 611130, China; National Demonstration Center for Experimental Animal Education, Chengdu 611130, China.
Vet Microbiol. 2023 Oct;285:109848. doi: 10.1016/j.vetmic.2023.109848. Epub 2023 Sep 7.
Interferon-γ (IFN-γ) is a pleiotropic cytokine that regulates diverse biological functions, including modulation of inflammatory response and innate and adaptive immunity. In our study, we found that IFN-γ plays an important role in the regulation of Pasteurella multocida toxin-associated pneumonia. In work described here, we demonstrated that rPMT induced a lethal pneumonia in WT mice and the severity of the pneumonia was substantially alleviated in IFN-γ-deficient mice, IFN-γ deficiency significantly elevated the survival rate and reduced the pathological lesions of the lungs after rPMT challenged. Notably, IFN-γ deficiency significantly decreased myeloperoxidase (MPO) expression abundance in the lung tissue, and the MPO was mainly expressed in the lung tissue injury region of WT mice. More importantly, IFN-γ deficiency impaired the activation of PANoptosis specific markers, including the caspase 3, GSDMD, and MLKL, and reduced the expression of IL-1β. Cumulatively, this study demonstrates that IFN-γ promotes PANoptosis in PMT induced pneumonia in mice, providing a basis for studying the pathogenic mechanism of PMT.
干扰素-γ（IFN-γ）是一种多功能细胞因子，调节多种生物功能，包括炎症反应和先天及适应性免疫的调节。在我们的研究中，我们发现 IFN-γ在多杀巴斯德氏菌毒素相关肺炎的调控中发挥重要作用。在本研究中，我们证明了 rPMT 在 WT 小鼠中引起致死性肺炎，IFN-γ 缺陷小鼠的肺炎严重程度显著减轻，IFN-γ 缺陷显著提高 rPMT 攻击后的存活率，并减少肺部的病理损伤。值得注意的是，IFN-γ 缺陷显著降低了肺组织中髓过氧化物酶（MPO）的表达丰度，MPO 主要表达在 WT 小鼠的肺组织损伤区域。更重要的是，IFN-γ 缺陷损害了 PANoptosis 特异性标志物的激活，包括 caspase 3、GSDMD 和 MLKL，并降低了 IL-1β的表达。综上所述，这项研究表明 IFN-γ 促进了 PMT 诱导的肺炎中的 PANoptosis，为研究 PMT 的致病机制提供了依据。
