Caspase-11 Non-canonical Inflammasomes in the Lung

Oh, Changhoon; Verma, Ashwani Kumar; Aachoui, Youssef

doi:10.3389/fimmu.2020.01895

Cited by 21 publications

(24 citation statements)

References 105 publications

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“…S. flexneri, a hexa-acylated lipid A-expressing bacterium, invades host cells and uses its T3SS to rapidly escape a phagosomal vacuole to establish a replicative niche within the cytosol. Caspase-11 and its human orthologs caspase-4 and -5 detect cytosolic LPS and trigger gasdermin D-dependent pyroptosis to eliminate intra-cytoplasmic bacterial threats ( Oh et al., 2020 ). However, the role of caspase-11 in S. flexneri defense is still unclear.…”

Section: Resultsmentioning

confidence: 99%

“…The host cytosol is a nutrient-rich environment that can be an ideal niche for pathogen replication ( Ray et al., 2009 ). However, the cytosol is also heavily guarded by several innate immune mechanisms, including cell autonomous responses mediated by interferon-stimulated genes including guanylate-binding proteins (GBPs) and inflammasome responses mediated by NOD-like receptors (NLRs) and inflammatory caspases (caspase-1 and -11) ( Oh et al., 2020 ; Randow et al., 2013 ). Due to these host defenses, few pathogens succeed in adopting the cytosol as a replication niche.…”

Section: Introductionmentioning

confidence: 99%

“…The NLRP3 inflammasome senses cytosolic perturbations indicative of catastrophic cellular events such as membrane pore formation or mitochondrial dysfunction ( Swanson et al., 2019 ). Upon detection, NAIP/NLRC4 and NLRP3 signal to caspase-1, whereas caspase-11 initiates its own oligomerization and auto-activation ( Oh et al., 2020 ; Shi et al., 2014 ). Regardless of the activating sensors, both caspases cleave and activate the pore-forming protein gasdermin D, resulting in pyroptosis ( He et al., 2015 ; Kayagaki et al., 2015 ; Shi et al., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Shigella OspC3 suppresses murine cytosolic LPS sensing

Verma

Hafeez

et al. 2021

iScience

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Summary Shigella flexneri , a cytosol-invasive gram-negative pathogen, deploys an array of type III-secreted effector proteins to evade host cell defenses. Caspase-11 and its human ortholog caspase-4 detect cytosolic lipopolysaccharide (LPS) and trigger gasdermin D-mediated pyroptosis to eliminate intra-cytoplasmic bacterial threats . However, the role of caspase-11 in combating S. flexneri is unclear. The Shigella T3SS effector OspC3 reportedly suppresses cytosolic LPS sensing by inhibiting caspase-4 but not caspase-11 activity. Surprisingly, we found that S. flexneri also uses OspC3 to inhibit murine caspase-11 activity. Mechanistically, we found that OspC3 binds only to primed caspase-11. Importantly, we demonstrate that S. flexneri employs OspC3 to prevent caspase-11-mediated pyroptosis in neutrophils, enabling bacteria to disseminate and evade clearance following intraperitoneal challenge. In contrast, S. flexneri lacking OspC3 is attenuated in a caspase-11- and gasdermin D-dependent fashion. Overall, our study reveals that OspC3 suppresses cytosolic LPS detection in a broad array of mammals.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Shigella OspC3 suppresses murine cytosolic LPS sensing

Verma

Hafeez

et al. 2021

iScience

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“…In sharp contrast, a dysfunctional caspase-11 in 129Sv smoking mice showed that both mucus formation, index of bronchial inflammation, and collagen deposition, index of the pulmonary matrix alteration, were significantly reduced. Caspase-11, as well as the analogue human caspase-4, have been already demonstrated as involved in lung inflammation [ 24 , 25 ]. We proved that caspase-4 is highly present in the blood of both smokers and COPD patients up to lung cancer patients, so that to identify it as a novel diagnostic tool to predict lung cancer establishment [ 11 , 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Caspase-11 and AIM2 inflammasome are involved in smoking-induced COPD and lung adenocarcinoma

et al. 2021

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Cigarette smoking is the leading risk factor for COPD and lung cancer establishment. Epidemiologically, COPD patients are 6.35 times more likely to develop lung cancer.To mimic COPD, we exposed mice to nose-only cigarette smoke and used human samples of lung adenocarcinoma patients according to the smoking and COPD status.Smoking C57Bl/6N mice had higher enlargement of alveoli, deposition of collagen and mucus production, associated to the release of IL-1-like cytokines, such as IL-1α and IL-1β at early time points and IL-18 at later time points. AIM2 expression was higher in lung recruited dendritic cells and macrophages in smoking mice, associated to the activation of caspase-11, rather than caspase-1. In support,129Sv mice, which are dysfunctional for caspase-11, had lower collagen deposition and mucus production, associated to lower release of IL-1-like and fibrotic TGFβ. Interestingly, higher expression of AIM2 in non-cancerous tissue of smoking COPD adenocarcinoma patients was correlated to a higher hazard ratio of poor survival rate than in patients who presented lower levels of AIM2.We found that AIM2 inflammasome is at the crossroad between COPD and lung cancer in that its higher presence is correlated to lower survival rate of smoking COPD adenocarcinoma patients.

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“…Non-canonical NLRP3 inflammasome mediated by CASP4/11 [80] has been shown to be activated by intestinal Gram-negative bacterial such as Citrobacter rodentium, Escherichia coli, Legionella pneumophila, Salmonella typhimurium, and Vibrio cholera [67] and other parasites such as Leishmania amazonensis [81]. The pathogen's LPS and other surface antigens have been associated with non-canonical NLRP3 inflammasome activation through interaction with Guanylate binding proteins (GBPs).…”

Section: Activation Of the Alveolar Nlrp3 Inflammasome During M Tuberculosis Infectionmentioning

confidence: 99%

Exploring the Use of Medicinal Plants and Their Bioactive Derivatives as Alveolar NLRP3 Inflammasome Regulators during Mycobacterium tuberculosis Infection

Mvubu

Chiliza

2021

IJMS

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Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a successful intracellular pathogen that is responsible for the highest mortality rate among diseases caused by bacterial infections. During early interaction with the host innate cells, M. tuberculosis cell surface antigens interact with Toll like receptor 4 (TLR4) to activate the nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3 (NLRP3) canonical, and non-canonical inflammasome pathways. NLRP3 inflammasome activation in the alveoli has been reported to contribute to the early inflammatory response that is needed for an effective anti-TB response through production of pro-inflammatory cytokines, including those of the Interleukin 1 (IL1) family. However, overstimulation of the alveolar NLRP3 inflammasomes can induce excessive inflammation that is pathological to the host. Several studies have explored the use of medicinal plants and/or their active derivatives to inhibit excessive stimulation of the inflammasomes and its associated factors, thus reducing immunopathological response in the host. This review describes the molecular mechanism of the NLRP3 inflammasome activation in the alveoli during M. tuberculosis infection. Furthermore, the mechanisms of inflammasome inhibition using medicinal plant and their derivatives will also be explored, thus offering a novel perspective on the alternative control strategies of M. tuberculosis-induced immunopathology.

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Caspase-11 Non-canonical Inflammasomes in the Lung

Cited by 21 publications

References 105 publications

Shigella OspC3 suppresses murine cytosolic LPS sensing

Shigella OspC3 suppresses murine cytosolic LPS sensing

Caspase-11 and AIM2 inflammasome are involved in smoking-induced COPD and lung adenocarcinoma

Exploring the Use of Medicinal Plants and Their Bioactive Derivatives as Alveolar NLRP3 Inflammasome Regulators during Mycobacterium tuberculosis Infection

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