2. Academic Validation
  3. RIP3 impedes Mycobacterium tuberculosis survival and promotes p62-mediated autophagy

RIP3 impedes Mycobacterium tuberculosis survival and promotes p62-mediated autophagy

  • Int Immunopharmacol. 2023 Jan 12;115:109696. doi: 10.1016/j.intimp.2023.109696.
Jiamei Zhang 1,  Lu Han 1,  Qinmei Ma 1,  Xiaoping Wang 2,  Jialin Yu 1,  Yanan Xu 1,  Xu Zhang 3,  Xiaoling Wu 4,  Guangcun Deng 5
Affiliations

Affiliations

  • 1 Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan, NingXia 750021, China; School of Life Science, NingXia University, Yinchuan, NingXia 750021, China.
  • 2 Tuberculosis Reference Laboratory, Ningxia Institute for Tuberculosis Control, The Fourth People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia 750021, China.
  • 3 Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
  • 4 Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan, NingXia 750021, China; School of Life Science, NingXia University, Yinchuan, NingXia 750021, China. Electronic address: wuxiaol@nxu.edu.cn.
  • 5 Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan, NingXia 750021, China; School of Life Science, NingXia University, Yinchuan, NingXia 750021, China. Electronic address: dgc@nxu.edu.cn.
PMID: 36638666 DOI: 10.1016/j.intimp.2023.109696
Abstract

Macrophage is believed to play a vital role in the fight against Mycobacterium tuberculosis (M.tb) Infection by activating Autophagy. Recently, receptor-interacting protein kinase-3 (RIP3), an essential kinase for necroptotic cell death signaling, has been demonstrated to be involved in Autophagy. However, RIP3's role in fighting against M.tb Infection remains elusive. Here we show that a substantial increase in inflammatory cell infiltration and higher Bacterial burden are observed in the lungs of RIP3-/- mice with Mycobacterium bovis Bacillus Calmette-Guerin (BCG) Infection. Meanwhile, RIP3 ameliorates lung injury and promote Autophagy via induce autophagosome and autophagolysosome formation which indicate that RIP3 is indispensable for host clearance of BCG via Autophagy. Mechanically, RIP3 enhances p62 binding to ubiquitylated proteins and LC3 by interacting with p62, and RHIM domain is required for RIP3-p62 interaction. Hence, our results conclusively show that RIP3 impedes M.tb survival and promotes p62-mediated Autophagy. The findings provide further insight into understanding the mechanism of M.tb immune escape and pathogenesis of tuberculosis.

Keywords

Autophagy; BCG; Macrophage; RIP3; p62.

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