Immunity against <i>Moraxella catarrhalis</i> requires guanylate‐binding proteins and caspase‐11‐<scp>NLRP3</scp> inflammasomes

Tuipulotu, Daniel Enosi; Feng, Shouya; Pandey, Abhimanu; Zhao, Anyang; Ngo, Chinh; Mathur, Anukriti; Lee, Jiwon; Shen, Cheng; Fox, Daniel; Xue, Yansong; Kay, Callum; Kirkby, Max; Pilato, Jordan Lo; Kaakoush, Nadeem O.; Webb, Daryl; Rug, Melanie; Robertson, Avril A. B.; Tessema, Melkamu B.; Pang, Stanley; Degrandi, Daniel; Pfeffer, Klaus; Augustyniak, Daria; Blumenthal, Antje; Miosge, Lisa A.; Brüstle, Anne; Yamamoto, Masahiro; Reading, Patrick C.; Burgio, Gaétan; Man, Si Ming

doi:10.15252/embj.2022112558

Cited by 14 publications

(4 citation statements)

References 95 publications

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“…Unlike human GBP1, our data therefore suggest that mouse GBP1 mechanism of resistance does not result in a direct binding of human GBP1 to LPS 20,31 . Our finding is in line with previous studies on Neisseria meningitidis 32 and Moraxella catarrhalis LOS 45 and E. coli LPS 46 , demonstrating no direct interaction between mouse GBP1 and the LOS.…”

Section: Our Findings Demonstrated That Recognition Of Mdr a Baumanni...supporting

confidence: 93%

Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii

Burgio,

Li,

Starrs

et al. 2024

Preprint

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Multidrug-resistant (MDR) Acinetobacter baumannii are of major concern worldwide due to their resistance to last resort carbapenem and polymyxin antibiotics. To develop an effective treatment strategy, it is critical to better understand how an A. baumannii MDR bacterium interacts with its mammalian host. Pattern-recognition receptors sense microbes, and activate the inflammasome pathway, leading to pro-inflammatory cytokine production and programmed cell death. Here, we examined the effects of a systemic MDR A. baumannii infection and found that MDR A. baumannii activate the NLRP3 inflammasome complex predominantly via the non-canonical caspase-11-dependent pathway. We show that caspase-1 and caspase-11-deficient mice are protected from a virulent MDR A. baumannii strain by maintaining a balance between protective and deleterious inflammation. Caspase-11-deficient mice also compromise between effector cell recruitment, phagocytosis, and programmed cell death in the lung during infection. Importantly, we found that cytosolic immunity - mediated by guanylate-binding protein 1 (GBP1) and type I interferon signalling - orchestrates caspase-11-dependent inflammasome activation. Together, our results suggest that non-canonical inflammasome activation via the IFN pathway plays a critical role in the host response against MDR A. baumannii infection.

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Section: Our Findings Demonstrated That Recognition Of Mdr a Baumanni...supporting

confidence: 93%

Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii

Burgio,

Li,

Starrs

et al. 2024

Preprint

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“…Lipid A is recognized not only by TLR4 but also by caspase-11, an intracellular LPS receptor (14). Caspase-11 is defined as a non-canonical NLRP3 inflammasome because it not only activates the canonical NLRP3 inflammasome but also induces pyroptosis (gasdermin D-dependent cell death) independent of NLRP3 (27,28). The present study revealed that ALN did not upregulate caspase-11 expression in RAW264 cells but di augment lipid A-induced IL-1β release by caspase-11 knockout RAW264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

Alendronate augments lipid A‑induced IL‑1β release by ASC‑deficient RAW264 cells via AP‑1 activation

Watanabe,

Tamai,

Kiyoura

2023

Exp Ther Med

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Alendronate (ALN) is an anti-bone-resorptive drug with inflammatory side effects. ALN upregulates lipid A-induced interleukin (IL)-1α and IL-1β release by J774.1 cells via apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) activation. The present study examined whether ALN augmented lipid A-induced proinflammatory cytokine production using ASC-deficient mouse macrophage-like RAW264 cells. Pretreatment of RAW264 cells with ALN significantly augmented lipid A-induced IL-1β release, although ALN did not upregulate the expression of Toll-like receptor 4, myeloid differentiation factor 88 (MyD88) and caspase-11. Moreover, pretreatment of caspase-11-deficient RAW264.7 cells with ALN significantly augmented lipid A-induced IL-1β release. Notably, ALN upregulated the activation of FosB, c-Jun or JunD, but not c-Fos or NF-κB in RAW264 cells. Furthermore, pretreatment with the activator protein 1 (AP-1) inhibitor SR11302, but not the c-Fos inhibitor T-5224, before addition of ALN inhibited ALN-augmented IL-1β release by lipid A-treated RAW264 cells. SR11302 also reduced ALN-augmented lactate dehydrogenase release by the cells. These findings collectively suggested that ALN augmented lipid A-induced IL-1β release and cell membrane damage in ASC-deficient RAW264 cells via activation of AP-1, but not NF-κB.

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“…THP‐1 monocytes and macrophages were primed using 500 ng/ml ultrapure LPS from E. coli for 3 h. Cells were treated with 36 μg/ml of lecithinase or 10 μM nigericin. For inhibition experiments, THP1 cells were pretreated for 30 min with 20 μM of MCC950 (Enosi Tuipulotu et al , 2023 ). PBMCs were primed using 1 μg/ml Pam3CSK4 (tlrl‐pms, InvivoGen) for 3 h, pretreated with or without 20 μM MCC950 for 30 min, and then stimulated with 1.5 × 10 −3 Units/ml lecithinase or 10 μM nigericin (N7143, Sigma) for 1 h. Cell culture supernatants were collected for ELISA and LDH assays.…”

Section: Methodsmentioning

confidence: 99%

Clostridium perfringens virulence factors are nonredundant activators of the NLRP3 inflammasome

et al. 2023

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Inflammasome signaling is a central pillar of innate immunity triggering inflammation and cell death in response to microbes and danger signals. Here, we show that two virulence factors from the human bacterial pathogen Clostridium perfringens are nonredundant activators of the NLRP3 inflammasome in mice and humans. C. perfringens lecithinase (also known as phospolipase C) and C. perfringens perfringolysin O induce distinct mechanisms of activation. Lecithinase enters LAMP1+ vesicular structures and induces lysosomal membrane destabilization. Furthermore, lecithinase induces the release of the inflammasome‐dependent cytokines IL‐1β and IL‐18, and the induction of cell death independently of the pore‐forming proteins gasdermin D, MLKL and the cell death effector protein ninjurin‐1 or NINJ1. We also show that lecithinase triggers inflammation via the NLRP3 inflammasome in vivo and that pharmacological blockade of NLRP3 using MCC950 partially prevents lecithinase‐induced lethality. Together, these findings reveal that lecithinase activates an alternative pathway to induce inflammation during C. perfringens infection and that this mode of action can be similarly exploited for sensing by a single inflammasome.

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Immunity against Moraxella catarrhalis requires guanylate‐binding proteins and caspase‐11‐NLRP3 inflammasomes

Cited by 14 publications

References 95 publications

Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii

Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii

Alendronate augments lipid A‑induced IL‑1β release by ASC‑deficient RAW264 cells via AP‑1 activation

Clostridium perfringens virulence factors are nonredundant activators of the NLRP3 inflammasome

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