Oncotarget

Research Papers: Immunology:

AIM2 inhibits autophagy and IFN-β production during M. bovis infection

Chunfa Liu, Ruichao Yue, Yang Yang, Yongyong Cui, Lifeng Yang, Deming Zhao and Xiangmei Zhou _

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Oncotarget. 2016; 7:46972-46987. https://doi.org/10.18632/oncotarget.10503

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Abstract

Chunfa Liu1, Ruichao Yue1, Yang Yang2, Yongyong Cui1, Lifeng Yang1, Deming Zhao1 and Xiangmei Zhou1

1 State Key Laboratories for Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China

2 College of Animal Sciences and Technology, Zhejiang A&F University, Lin’an, China

Correspondence to:

Xiangmei Zhou, email:

Keywords: M. bovis, autophagy, AIM2 inflammasome, STING, Immunology and Microbiology Section, Immune response, Immunity

Received: March 21, 2016 Accepted: June 06, 2016 Published: July 09, 2016

Abstract

Mycobacteria can trigger the AIM2 inflammasome, autophagy activation and type-I interferon release, which are both activated by cytosolic DNA. We have recently demonstrated that activation of the AIM2 inflammasome during M. bovis infection is the result of mycobacterial translocation into the cytosol. To elucidate the effects of inflammasome activation on autophagy, we investigated the role of the AIM2 inflammasome from macrophages infected with a virulent strain of M. bovis. The results showed that the M. bovis-induced AIM2 inflammasome activation decreases autophagy in immortalized and primary murine macrophages. This relied on the inflammasome sensor AIM2 which conjugates with cytosolic DNA to inhibit the STING-dependent pathway involved in selective autophagy and interferon-β release in Mycobacterium-infected macrophages. These results suggest that the AIM2 cytosolic DNA sensor may conjugate competitively with cytosolic M. bovis DNA to restrict M. bovis induced STING-TBK1-dependent autophagy activation and IFN-β secretion.


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