Francisella infection triggers activation of the AIM2 inflammasome in murine dendritic cells

Belhocine, Kamila; Monack, Denise M.

doi:10.1111/j.1462-5822.2011.01700.x

Cited by 54 publications

(46 citation statements)

References 48 publications

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“…However, there are few studies describing the mechanisms of AIM2 activation triggered by bacterial infection in dendritic cells. One study performed with intracellular Francisella tularensis observed that this bacterium was able to activate the AIM2 inflammasome in dendritic cells (DCs) causing release of large amounts of IL-1β and host cell death [29]. Moreover, AIM2-deficient mice displayed increased susceptibility to Francisella infection compared to wild-type mice [14].…”

Section: Introductionmentioning

confidence: 99%

The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection

et al. 2016

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The innate immune system is essential for detection and elimination of bacterial pathogens. Upon inflammasome activation, caspase-1 cleaves pro-IL-1β and pro-IL-18 to their mature forms IL-1β and IL-18, respectively, and the cell undergoes inflammatory death termed pyroptosis. Here we reviewed recent findings demonstrating that Brucella abortus ligands activate NLRP3 and AIM2 inflammasomes which leads to control of infection. This protective effect is due to inflammatory response caused by IL-1β and IL-18 rather than cell death. Brucella DNA is sensed by AIM2 and bacteria induced mitochondrial reactive oxygen species is detected by NLRP3. However, deregulation of proinflammatory cytokine production can lead to immunopathology. Nervous system invasion by bacteria of the genus Brucella results in an inflammatory disorder termed neurobrucellosis. Herein we discuss the mechanism of caspase-1 activation and IL-1β secretion in glial cells infected with B. abortus. Our results demonstrate that the ASC inflammasome is indispensable for inducing the activation of caspase-1 and secretion of IL-1β upon infection of astrocytes and microglia with Brucella. Moreover, our results demonstrate that secretion of IL-1β by Brucella-infected glial cells depends on NLRP3 and AIM2 and leads to neurobrucellosis. Further, the inhibition of the host cell inflammasome as an immune evasion strategy has been described for bacterial pathogens. We discuss here that the bacterial type IV secretion system VirB is required for inflammasome activation in host cells during infection. Taken together, our results indicate that Brucella is sensed by ASC inflammasomes mainly NLRP3 and AIM2 that collectively orchestrate a robust caspase-1 activation and proinflammatory response.

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Section: Introductionmentioning

confidence: 99%

The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection

et al. 2016

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“…Assembly and thereby the activation of the inflammasome induces the cleavage and activation of caspase-1, which promotes the processing and secretion of the active IL-1b and IL-18 (9). Besides, caspase-1 also induces pyroptosis, an inflammation-associated form of cell death, in different cell types including DCs (10).…”

mentioning

confidence: 99%

Helicobacter pylori–Induced IL-1β Secretion in Innate Immune Cells Is Regulated by the NLRP3 Inflammasome and Requires the Cag Pathogenicity Island

Semper

Mejías-Luque

Groß

et al. 2014

The Journal of Immunology

105

115

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Infection with the gram-negative bacterium Helicobacter pylori is the most prevalent chronic bacterial infection, affecting ∼50% of the world’s population, and is the main risk factor of gastric cancer. The proinflammatory cytokine IL-1β plays a crucial role in the development of gastric tumors and polymorphisms in the IL-1 gene cluster leading to increased IL-1β production have been associated with increased risk for gastric cancer. To be active, pro–IL-1β must be cleaved by the inflammasome, an intracellular multiprotein complex implicated in physiological and pathological inflammation. Recently, H. pylori was postulated to activate the inflammasome in murine bone marrow–derived dendritic cells; however, the molecular mechanisms as well as the bacterial virulence factor acting as signal 2 activating the inflammasome remain elusive. In this study, we analyzed the inflammasome complex regulating IL-1β upon H. pylori infection as well as the molecular mechanisms involved. Our results indicate that H. pylori–induced IL-1β secretion is mediated by activation of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain–containing 3 inflammasome. We also show that reactive oxygen species, potassium efflux, and lysosomal destabilization are the main cellular mechanisms responsible of nucleotide-binding oligomerization domain family, pyrin domain–containing 3 inflammasome activation upon H. pylori infection, and identify vacuolating cytotoxin A and cag pathogenicity island as the bacterial virulence determinants involved. Moreover, in vivo experiments indicate an important role for the inflammasome in the onset and establishment of H. pylori infection and in the subsequent inflammatory response of the host.

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“…Interestingly, studies have noted that type I IFNsignaling is necessary for inflammasome activation in response to cytosolic Listeria monocytogenes (Henry and others 2007;Belhocine and Monack 2011). These studies also showed specific connections between type I IFN-signaling and inflammasome activation.…”

Section: Cytoplasmic Nucleic Acid Sensorsmentioning

confidence: 88%

Interferons in Autoimmune and Inflammatory Diseases: Regulation and Roles

Choubey

Moudgil

2011

Journal of Interferon & Cytokine Research

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Several lines of evidence strongly implicate type I interferons (IFN-a and b) and IFN-signaling in the pathogenesis of certain autoimmune inflammatory diseases. Accordingly, genome-wide association studies have identified polymorphisms in the type I IFN-signaling pathways. Other studies also indicate that a feed-forward loop of type I IFN production, which involves sensing of cytoplasmic nucleic acids by sensors, contributes to the development of immunopathology. In addition, a mutually positive regulatory feedback loop between type I IFNs and estrogen receptor-a may contribute to a gender bias, thus resulting in an increased production of type I IFNs and associated immunopathology in women. Increased levels of type I IFNs have numerous immunomodulatory functions for both the innate and adaptive immune responses. Given that the IFN-b also has some anti-inflammatory roles, identifying molecular links among certain genotypes, cytokine profiles, and associated phenotypes in patients with autoimmune inflammatory diseases is likely to improve our understanding of autoimmunity-associated pathogenesis and suboptimal outcomes following standard therapies.

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Francisella infection triggers activation of the AIM2 inflammasome in murine dendritic cells

Cited by 54 publications

References 48 publications

The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection

The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection

Helicobacter pylori–Induced IL-1β Secretion in Innate Immune Cells Is Regulated by the NLRP3 Inflammasome and Requires the Cag Pathogenicity Island

Interferons in Autoimmune and Inflammatory Diseases: Regulation and Roles

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