Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis

Liu, Yang; Lü, Xing; Li, Fen-Xin; Wang, Na; Ma, Yuze; Li, Jianwei; Wu, Yujing; Liang, Jing; Lei, Yu-Xin; Wang, Xueyin; Fan-hua, Meng; Yang, Yongjun; Li, Guangpeng; Wang, Xiao; Yu, Shui-Xing

doi:10.1016/j.isci.2022.105121

Cited by 9 publications

(17 citation statements)

References 46 publications

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“…However, the effect of IL-18 in microbial infections varies . It can be both beneficial ,,, and detrimental , to the host, probably relying on the experiment process. We suspected whether the defect of IL-18 release may result in susceptibility to infection in the absence of Gpr120 .…”

Section: Discussionmentioning

confidence: 99%

“…The C. perfringens enterocolitis model was established as previously described. 6 Age-and sex-matched mice were administered with D-4-amino-3-isoxazolidinone (0.4 mg per mouse) prior to oral inoculation of the log-phase C. perfringens strain CP1 (1 × 10 8 or 2 × 10 8 CFUs per mouse). To induce gas gangrene, age-and sex-matched mice were intramuscularly challenged with 1 × 10 7 or 5 × 10 7 CFUs of log-phase C. perfringens strain CP1, and the severity of gas gangrene was assessed using a scoring system as previously reported.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…The C. perfringens enterocolitis model was established as previously described . Age- and sex-matched mice were administered with d -4-amino-3-isoxazolidinone (0.4 mg per mouse) prior to oral inoculation of the log-phase C.…”

Section: Methodsmentioning

confidence: 99%

“…5 Previously, we also provided evidence demonstrating that mixed lineage kinaselike protein (MLKL) contributes to host protection against C. perfringens invasion via facilitating NLRP3 inflammasomeextracellular traps axis. 6 Therefore, it is not surprising that exploring the innate immunity mechanisms of host combat against C. perfringens will be conducive to the development of new strategies for the effective control of C. perfringens infection.…”

Section: ■ Introductionmentioning

confidence: 99%

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G Protein-Coupled Receptor 120 Mediates Host Defense against Clostridium perfringens Infection through Regulating NOD-like Receptor Family Pyrin Domain-Containing 3 Inflammasome Activation

Liu

Lei

et al. 2023

J. Agric. Food Chem.

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Clostridium perfringens is a major cause of infectious foodborne disease, frequently associated with the consumption of raw and undercooked food. Despite intensive studies on clarifying C. perfringens pathogenesis, the molecular mechanisms of host− pathogen interactions remain poorly understood. In soft tissue and mucosal infection models, Gpr120 -/mice, G protein-coupled receptor 120 (GPR120), are more susceptible to C. perfringens infection. Gpr120 deficiency leads to a low survival rate (30 and 10%, p < 0.01), more bacterial loads in the muscle (2.26 × 10 8 ± 2.08 × 10 8 CFUs/g, p < 0.01), duodenum (2.80 × 10 7 ± 1.61 × 10 7 CFUs/g, p < 0.01), cecum (2.50 × 10 8 ± 2.05 × 10 8 CFUs/g, p < 0.01), and MLN (1.23 × 10 6 ± 8.06 × 10 5 CFUs/g, p < 0.01), less IL-18 production in the muscle (8.54 × 10 3 ± 1.20 × 10 3 pg/g, p < 0.01), duodenum (3.34 × 10 3 ± 2.46 × 10 2 pg/g, p < 0.01), and cecum (3.81 × 10 3 ± 5.29 × 10 2 pg/g, p < 0.01), and severe organ injury. Obviously, GPR120 facilitates IL-18 production and pathogen control via potassium efflux-dependent NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling. Mechanistically, GPR120 interaction with NLRP3 potentiates the NLRP3 inflammasome assembly. Thus, this study uncovers a novel role of GPR120 in host protection and reveals that GPR120 may be a potential therapeutic target for limiting pathogen infection.

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Section: Discussionmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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G Protein-Coupled Receptor 120 Mediates Host Defense against Clostridium perfringens Infection through Regulating NOD-like Receptor Family Pyrin Domain-Containing 3 Inflammasome Activation

Liu

Lei

et al. 2023

J. Agric. Food Chem.

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“…MLKL plays an important role in innate immunity during the process of necroptosis. Regarding C. perfringens , MLKL promoted bacterial eradication, increased host survival and resolution of inflammation, demonstrating that MLKL-NLRP3 inflammasome confers protection to invading pathogens ( 160 ).…”

Section: Gram-positive Bacteria Trigger Inflammasome Activationmentioning

confidence: 99%

Inflammasome activation by Gram-positive bacteria: Mechanisms of activation and regulation

Keestra-Gounder

Nagao

2023

Front. Immunol.

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The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens. Activaton of the receptor leads to formation of the inflammasomes and subsequent processing and activation of caspase-1 that cleaves the proinflammatory cytokines IL-1β and IL-18. Active caspase-1, and in some instances caspase-11, cleaves gasdermin D that translocates to the cell membrane where it forms pores resulting in the cell death program called pyroptosis. Inflammasomes can detect a range of microbial ligands through direct interaction or indirectly through diverse cellular processes including changes in ion fluxes, production of reactive oxygen species and disruption of various host cell functions. In this review, we will focus on the NLRP3, NLRP6, NLRC4 and AIM2 inflammasomes and how they are activated and regulated during infections with Gram-positive bacteria, including Staphylococcus spp., Streptococcus spp. and Listeria monocytogenes.

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The protective effects of Bacillus licheniformis against inflammatory responses and intestinal barrier damage in broilers with necrotic enteritis induced by Clostridium perfringens

Zhang

Qin²,

Yang

et al. 2023

J Sci Food Agric

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BackgroundBacillus licheniformis is a gram‐positive bacterium that has strong environmental adaptability and can improve the growth performance, immunity, and antioxidant function of broilers. The current study aimed to elucidate the protective capability of B. licheniformis against inflammatory responses and intestinal barrier damage in broilers with necrotic enteritis (NE) induced by Clostridium perfringens (CP).ResultsThe results showed that B. licheniformis enhanced the final body weight in broilers compared with that of broilers in the CP group after the stress of infection (P < 0.05). Bacillus licheniformis reversed the decreased levels of serum and jejunum mucosa immunoglobulins and anti‐inflammatory cytokines, reduced the values of villus height and the ratio of villus height to crypt depth, and mitigated the increased levels of serum d‐lactic acid and diamine oxidase in CP‐challenged broilers (P < 0.05). Moreover, B. licheniformis modulated the expression levels of genes involved in the TLR4/NF‐κB signalling pathway, the NLRP3 inflammasome activation pathway, and the sirt 1/Parkin signalling pathway in CP‐challenged broilers. Compared with the CP challenge group, the B. licheniformis‐treated group exhibited reduced abundance values of Shuttleworthia and Alistipes and enhanced abundance values of Parabacteroides in the caecal contents (P < 0.05).ConclusionBacillus licheniformis improved the final body weight and alleviated the inflammatory response and intestinal barrier function damage in birds with NE induced by CP by maintaining intestinal physiological function, enhancing immunity, regulating inflammatory cytokine secretion, modulating the mitophagy response, and increasing the abundance of beneficial intestinal flora. © 2023 Society of Chemical Industry.

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Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis

Cited by 9 publications

References 46 publications

G Protein-Coupled Receptor 120 Mediates Host Defense against Clostridium perfringens Infection through Regulating NOD-like Receptor Family Pyrin Domain-Containing 3 Inflammasome Activation

G Protein-Coupled Receptor 120 Mediates Host Defense against Clostridium perfringens Infection through Regulating NOD-like Receptor Family Pyrin Domain-Containing 3 Inflammasome Activation

Inflammasome activation by Gram-positive bacteria: Mechanisms of activation and regulation

The protective effects of Bacillus licheniformis against inflammatory responses and intestinal barrier damage in broilers with necrotic enteritis induced by Clostridium perfringens

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