title: AIM2 inhibits autophagy and IFN-β production during M. bovis infection.
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.
authors.affiliation: 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.
authors.forename: Chunfa
authors.initials: C
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Ruichao
authors.initials: R
authors.lastname: Yue
authors.affiliation: College of Animal Sciences and Technology, Zhejiang A&F University, Lin'an, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: 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.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D020170:Caspase 1 / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D005260:Female; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology* / Q000378:metabolism; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000276:immunology; D014380:Tuberculosis, Bovine / Q000276:immunology* / Q000382:microbiology; D000099197:STING Protein
chemical_list: D020170:Caspase 1; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D016899:Interferon-beta; D053583:Interleukin-1beta; D008565:Membrane Proteins; C540422:Aim2 protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein
keywords: AIM2 inflammasome; Immune response; Immunity; Immunology and Microbiology Section; M. bovis; STING; autophagy