The Gasdermin‐D pore acts as a conduit for IL‐1β secretion in mice

Heilig, Rosalie; Dick, Mathias S.; Sborgi, Lorenzo; Meunier, Étienne; Hiller, Sebastian; Brož, Petr

doi:10.1002/eji.201747404

Cited by 291 publications

(309 citation statements)

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“…This autoregulated protein is responsible for pyroptosis and is active only when processed by caspase-1 or caspase-11 [51,52]. However, recent reports have described gasdermin D processing and the formation of membrane pores to allow IL-1β secretion without inducing pyroptosis [53,54]. The decision between killing the cell or allowing IL-1β secretion might depend on the strength of the signal that promotes inflammasome activation and gasdermin D processing.…”

Section: Discussionmentioning

confidence: 99%

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

et al. 2018

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B cells are a target of Salmonella infection, allowing bacteria survival without inducing pyroptosis. This event is due to downregulation of Nlrc4 expression and lack of inflammasome complex activation, which impairs the secretion of IL-1β. YAP phosphorylation is required for downregulation of Nlrc4 in B cells during Salmonella infection; however, the microorganism’s mechanisms underlying the inhibition of the NLRC4 inflammasome in B cells are not fully understood. Our findings demonstrate that the Salmonella effector SopB triggers a signaling cascade involving PI3K, PDK1 and mTORC2 that activates Akt with consequent phosphorylation of YAP. When we deleted sopB in Salmonella, infected B cells that lack Rictor, or inhibited the signaling cascade using a pharmacological approach, we were able to restore the function of the NLRC4 inflammasome in B cells and the ability to control the infection. Furthermore, B cells from infected mice exhibited activation of Akt and YAP phosphorylation, suggesting that Salmonella also triggers this pathway in vivo. In summary, our data demonstrate that the Salmonella effector inositide phosphate phosphatase SopB triggers the PI3K-Akt-YAP pathway to inhibit the NLRC4 inflammasome in B cells. This study provides further evidence that Salmonella triggers cellular mechanisms in B lymphocytes to manipulate the host environment by turning it into a survival niche to establish a successful infection.

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Section: Discussionmentioning

confidence: 99%

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

et al. 2018

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“…In response to pathogen‐associated molecular patterns and damage‐associated molecular patterns, some of NLRs and PYHIN proteins are able to assemble multiprotein platforms called inflammasomes . Canonical inflammasomes recruit and activate inflammatory caspase‐1, that, in turn, promotes maturation and secretion of the proinflammatory cytokines IL‐1β and IL‐18 and initiates a Gasdermin‐D‐mediated cell death, termed pyroptosis . Previous data, including ours, described the involvement of NLR‐pyrin domain containing 3 protein (NLRP3) in the control of T. cruzi .…”

Section: Introductionmentioning

confidence: 85%

Frontline Science: Autophagy is a cell autonomous effector mechanism mediated by NLRP3 to control Trypanosoma cruzi infection

Matteucci

Pereira

Weinlich

et al. 2019

Journal of Leukocyte Biology

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Autophagy and inflammasome activation are cell‐autonomous and cross‐regulated processes involved in host resistance against infections. Our group previously described that NLRP3 inflammasome is required for the control of Trypanosoma cruzi, the causative agent of Chagas disease. However, the involvement of autophagy in this process was unclear. Here, we demonstrated that T. cruzi was able to induce an increase in LC3‐II expression as well as autophagosome and autolysosome formation in peritoneal macrophages (PMs) from C57BL/6 wild‐type mice. Moreover, the pharmacologic inhibition of autophagic machinery impaired the ability of PMs to control T. cruzi replication. Importantly, NLRP3 was required for the induction of a regular autophagic flux in response to T. cruzi, an effect mediated by its participation in the autolysosomes formation. Together, these results indicate autophagy as an effector mechanism mediated by NLRP3 to control T. cruzi infection.

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“…Upon cleavage, GSDMD releases an N‐terminal fragment that oligomerizes and forms pore‐like structures within the membrane lipid bilayer. These pores have been proposed to function as conduits for the release of small proteins including IL‐1β and IL‐18 …”

Section: Inflammatory Signals Triggered By Inflammasome Activationmentioning

confidence: 99%

Inflammasomes contributing to inflammation in arthritis

Spel

Martinon

2020

Immunological Reviews

108

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Inflammasomes are intracellular multiprotein signaling platforms that initiate inflammatory responses in response to pathogens and cellular damage. Active inflammasomes induce the enzymatic activity of caspase‐1, resulting in the induction of inflammatory cell death, pyroptosis, and the maturation and secretion of inflammatory cytokines IL‐1β and IL‐18. Inflammasomes are activated in many inflammatory diseases, including autoinflammatory disorders and arthritis, and inflammasome‐specific therapies are under development for the treatment of inflammatory conditions. In this review, we outline the different inflammasome platforms and recent findings contributing to our knowledge about inflammasome biology in health and disease. In particular, we discuss the role of the inflammasome in the pathogenesis of arthritic diseases, including rheumatoid arthritis, gout, ankylosing spondylitis, and juvenile idiopathic arthritis, and the potential of newly developed therapies that specifically target the inflammasome or its products for the treatment of inflammatory diseases.

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The Gasdermin‐D pore acts as a conduit for IL‐1β secretion in mice

Cited by 291 publications

References 50 publications

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

Frontline Science: Autophagy is a cell autonomous effector mechanism mediated by NLRP3 to control Trypanosoma cruzi infection

Inflammasomes contributing to inflammation in arthritis

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