title: Effects of Mycobacterium tuberculosis ESAT-6/CFP-10 fusion protein on the autophagy function of mouse macrophages.
abstract: Autophagy plays specific roles in host innate and adaptive immune responses to numerous intracellular pathogens, including Mycobacterium tuberculosis. The ESAT-6 and CFP-10 proteins are secreted by M. tuberculosis and play important roles in pathogenesis. We hypothesized that these two proteins may affect the autophagy function of host macrophages during infection with M. tuberculosis, thereby shaping the immune reaction toward the pathogen. Interestingly, we found that rapamycin-induced autophagy of macrophages infected with M. tuberculosis H37Rv enhanced localization of mycobacteria with autophagosomes and lysosomes. Ectopic expression of the ESAT-6/CFP-10 fusion in macrophages dramatically inhibited autophagosome formation, and M. tuberculosis survival inside infected macrophages was significantly affected as well. Further, M. tuberculosis viability was increased by the fusion protein. Expression levels of autophagy-related genes (ATG), especially atg8, also decreased (p<0.05). These results suggested that ESAT-6 and CFP-10 proteins play significant roles in autophagy formation in M. tuberculosis infection and that autophagosome formation is regulated through the expression of ATG.
authors: Department of Epidemiology, Fourth Military Medical University, 17 Changle West Road, Xi'an, Shaanxi Province, China.
authors: Lei
authors: L
authors: Zhang
authors: Hai
authors: H
authors: Zhang
authors: Yong
authors: Y
authors: Zhao
authors: Fengfeng
authors: F
authors: Mao
authors: Jing
authors: J
authors: Wu
authors: Bing
authors: B
authors: Bai
authors: Zhikai
authors: Z
authors: Xu
authors: Ying
authors: Y
authors: Jiang
authors: Changhong
authors: C
authors: Shi
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects
chemical_list: D000942:Antigens, Bacterial; C491971:Atg12 protein, mouse; C495773:Atg5 protein, mouse; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C505464:ESAT-6-CFP10 fusion protein; D008869:Microtubule-Associated Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins