The AIM2 Inflammasome Is Involved in Macrophage Activation During Infection With Virulent Mycobacterium bovis Strain

Yang, Yang; Zhou, Xiangmei; Kouadir, Mohammed; Shi, Fushan; Ding, Tianjian; Liu, Chunfa; Liu, Jin; Wang, Min; Yang, Lifeng; Yin, Xiaonan; Zhao, Deming

doi:10.1093/infdis/jit347

Cited by 52 publications

(59 citation statements)

References 44 publications

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“…Mtb and M. leprae can translocate from phagolysomes to the cytosol of myeloid cells in a RD1 (region of difference-1)-dependent manner [20]. These results are consistent with our results of M. bovis -induced activation of the AIM2 inflammasome following translocation of the bacteria from the phagosome to the cytosol [16]. In contrast, several reports have demonstrated that activation of autophagy by double-stranded DNA (dsDNA) from the avirulent BCG does not possess RD1 in an AIM2-dependent manner [21, 22].…”

Section: Introductionsupporting

confidence: 89%

“…Recent studies have shown that cytosolic DNA can activate autophagy [13]. Our previous results suggested that M. bovis can escape from the phagosome to the cytosol [16] and we detected M. bovis DNA in the cytosol at 24 h post-infection (Figure 1c). …”

Section: Resultssupporting

confidence: 64%

“…The gene expression of AIM2 affects the cleavage of caspase-1 during M. bovis infection [16]. We tested LC3-II expression in BMDMs after M. bovis infection in the presence or absence of the caspase-1 specific inhibitor, Z-YVAD-fmk (Figure 4a and 4b).…”

Section: Resultsmentioning

confidence: 99%

“…Several cytosolic bacterial pathogens have been demonstrated to be involved in AIM2 inflammasome activation [16–19]. Mtb and M. leprae can translocate from phagolysomes to the cytosol of myeloid cells in a RD1 (region of difference-1)-dependent manner [20].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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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Section: Introductionsupporting

confidence: 89%

Section: Resultssupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…They are molecular platforms activated upon infection or stress to trigger innate immune defenses through the maturation and secretion of pro-inflammatory cytokines such as IL-1b and IL-18. As far as we know, M. tuberculosis activates the NLRP3 and AIM2 inflammasomes (Dorhoi et al 2012;Mishra et al 2010;Saiga et al 2012), and M. bovis activates the AIM2 inflammasome (Yang et al 2013). Previous studies showed several signaling pathways play critical roles in activating the NLRP3 inflammasome, including K ?…”

Section: Introductionmentioning

confidence: 99%

Inflammasomes-dependent regulation of IL-1β secretion induced by the virulent Mycobacterium bovis Beijing strain in THP-1 macrophages

Zhou

Zhao

Yue

et al. 2015

Antonie van Leeuwenhoek

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Mycobacterium bovis is the causative agent of tuberculosis in cattle. Infection of macrophages with M. bovis leads to the activation of the "nucleotide binding and oligomerization, leucine-rich repeat and pyrin domains-containing protein 3" (NLRP3) and "absent in melanoma 2" (AIM2) inflammasomes, which in turn triggers release of the proinflammatory cytokine interleukin-1β (IL-1β) that contributes to bacterial clearance and plays a crucial role in the host defense. However, NLRP3 and AIM2 inflammasome activation is influenced by several factors and how IL-1β secretion by M. bovis-infected macrophages is regulated via the inflammasome pathway remains unclear. Here we found that IL-1β secretion and pro-IL-1β protein accumulation were inhibited in THP-1 macrophages upon exposure to the virulent M. bovis Beijing strain in the presence of high K(+) concentrations, cycloheximide (a protein synthesis inhibitor) and PR-619 (a deubiquitinating enzyme inhibitor). Scavenging reactive oxygen species (ROS) induced by N-acetylcysteine reduced IL-1β release independent of the mitochondrial permeability transition. Collectively, our results suggest that IL-1β secretion by M. bovis-infected THP-1 macrophages is reduced by high extracellular K(+) concentration, inhibition of new protein synthesis, deubiquitination, and ROS generation.

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AIM2 inflammasome in infection, cancer, and autoimmunity: Role in DNA sensing, inflammation, and innate immunity

2015

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Recognition of DNA by the cell is an important immunological signature that marks the initiation of an innate immune response. AIM2 is a cytoplasmic sensor that recognizes dsDNA of microbial or host origin. Upon binding to DNA, AIM2 assembles a multi-protein complex called the inflammasome, which drives pyroptosis and proteolytic cleavage of the pro-inflammatory cytokines pro-IL-1β and pro-IL-18. Release of microbial DNA into the cytoplasm during infection by Francisella, Listeria, Mycobacterium, mouse cytomegalovirus, vaccinia virus, Aspergillus and Plasmodium species leads to activation of the AIM2 inflammasome. In contrast, inappropriate recognition of cytoplasmic self-DNA by AIM2 contributes to the development of psoriasis, dermatitis, arthritis and other autoimmune and inflammatory diseases. Inflammasome-independent functions of AIM2 have also been described, including the regulation of the intestinal stem cell proliferation and the gut microbiota ecology in the control of colorectal cancer. In this review we provide an overview of the latest research on AIM2 inflammasome and its role in infection, cancer and autoimmunity.

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The AIM2 Inflammasome Is Involved in Macrophage Activation During Infection With Virulent Mycobacterium bovis Strain

Abstract: We conclude that the AIM2 inflammasome is involved in macrophage activation during infection with virulent M. bovis strain. To our knowledge, this is the first evidences for the involvement of the AIM2 inflammasome in M. bovis infection.

Cited by 52 publications

References 44 publications

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

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

Inflammasomes-dependent regulation of IL-1β secretion induced by the virulent Mycobacterium bovis Beijing strain in THP-1 macrophages

AIM2 inflammasome in infection, cancer, and autoimmunity: Role in DNA sensing, inflammation, and innate immunity

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