Vermeire Charlie A, Tan Xuejuan, Ramos-Leyva Aidaly, Wood Ava, Kotey Stephen K, Hartson Steven D, Liang Yurong, Liu Lin, Cheng Yong
Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma, USA.
Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, Oklahoma, USA.
Proteomics. 2025 Feb;25(3):e202400181. doi: 10.1002/pmic.202400181. Epub 2024 Sep 16.
Extracellular vesicles (EVs), such as exosomes, play a critical role in cell-to-cell communication and regulating cellular processes in recipient cells. Non-tuberculous mycobacteria (NTM), such as Mycobacterium abscessus, are a group of environmental bacteria that can cause severe lung infections in populations with pre-existing lung conditions, such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). There is limited knowledge of the engagement of EVs in the host-pathogen interactions in the context of NTM infections. In this study, we found that M. abscessus infection increased the release of a subpopulation of exosomes (CD9, CD63, and/or CD81 positive) by mouse macrophages in cell culture. Proteomic analysis of these vesicles demonstrated that M. abscessus infection affects the enrichment of host proteins in exosomes released by macrophages. When compared to exosomes from uninfected macrophages, exosomes released by M. abscessus-infected macrophages significantly improved M. abscessus growth and downregulated the intracellular level of glutamine in recipient macrophages in cell culture. Increasing glutamine concentration in the medium rescued intracellular glutamine levels and M. abscessus killing in recipient macrophages that were treated with exosomes from M. abscessus-infected macrophages. Taken together, our results indicate that exosomes may serve as extracellular glutamine eliminators that interfere with glutamine-dependent M. abscessus killing in recipient macrophages.
细胞外囊泡（EVs），如外泌体，在细胞间通讯和调节受体细胞的细胞过程中起着关键作用。非结核分枝杆菌（NTM），如脓肿分枝杆菌，是一类环境细菌，可在患有如囊性纤维化（CF）和慢性阻塞性肺疾病（COPD）等既往肺部疾病的人群中引起严重肺部感染。关于在NTM感染背景下EVs参与宿主-病原体相互作用的了解有限。在本研究中，我们发现脓肿分枝杆菌感染增加了细胞培养中小鼠巨噬细胞释放的外泌体亚群（CD9、CD63和/或CD81阳性）。对这些囊泡的蛋白质组学分析表明，脓肿分枝杆菌感染影响巨噬细胞释放的外泌体中宿主蛋白的富集。与未感染巨噬细胞的外泌体相比，脓肿分枝杆菌感染的巨噬细胞释放的外泌体在细胞培养中显著促进了脓肿分枝杆菌的生长，并下调了受体巨噬细胞内谷氨酰胺的水平。提高培养基中谷氨酰胺的浓度可挽救用脓肿分枝杆菌感染的巨噬细胞的外泌体处理的受体巨噬细胞内的谷氨酰胺水平和对脓肿分枝杆菌的杀伤作用。综上所述，我们的结果表明，外泌体可能作为细胞外谷氨酰胺清除剂，干扰受体巨噬细胞中谷氨酰胺依赖性的脓肿分枝杆菌杀伤作用。
