title: A Negative Feedback Loop Between Autophagy and Immune Responses in Mycobacterium leprae Infection.
abstract: The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level. However, macrophages with high autophagy levels preferentially expressed lower levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor-α, and preferentially primed anti-inflammatory T cells responses, characterized by high IL-10 and low interferon-γ, granzyme B, and perforin responses. These anti-inflammatory T cells could suppress further induction of autophagy, leading to improved survival of intracellular M. leprae in infected macrophages. Therefore, these data demonstrated that although autophagy had a role in eliminating intracellular pathogens, the induction of autophagy resulted in anti-inflammatory immune responses, which suppressed autophagy in a negative feedback loop and allowed the persistence of M. leprae.
authors.affiliation: 1 Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine , Shanghai, China .
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 1 Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine , Shanghai, China .
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 2 Shiping County People's Hospital , Yunnan, China .
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: 3 Yunnan Center for Disease Control and Prevention , Yunnan, China .
authors.forename: Tiejun
authors.initials: T
authors.lastname: Shui
authors.affiliation: 1 Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine , Shanghai, China .
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: 3 Yunnan Center for Disease Control and Prevention , Yunnan, China .
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: 4 DICAT Biomedical Computation Centre , Vancouver, British Columbia, Canada .
authors.forename: Joanna
authors.initials: J
authors.lastname: Yuan
authors.affiliation: 1 Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine , Shanghai, China .
authors.forename: Yeqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1 Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine , Shanghai, China .
authors.forename: Degang
authors.initials: D
authors.lastname: Yang
mesh_terms: D000818:Animals; D001343:Autophagy; D016207:Cytokines / Q000378:metabolism; D025461:Feedback, Physiological; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D009166:Mycobacterium leprae / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines
keywords: autophagy; immune response; leprosy