Defective apoptotic cell clearance activates innate immune response to protect <i>Caenorhabditis elegans</i> against pathogenic bacteria

Wan, Jinlong; Yuan, Lei; Jing, Huiru; Zheng, Qian; Xiao, Hui

doi:10.1080/21505594.2020.1857982

Cited by 7 publications

(4 citation statements)

References 44 publications

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“…To achieve inadequate clearance of apoptotic cells, Caenorhabditis elegans (C. elegans) stimulates the PMK-1 p38 MAPK and MPK-1/ERK MAPK pathways, which can support anti-microbial defense. For instance, apoptotic cell clearance mutant worms are more resistant to the pathogenic strains of Salmonella typhimurium SL1344 and Pseudomonas aeruginosa PA14 [68]. Ortiz, A. et al discovered that C. elegans' innate immune system reduces bacterial abundances through the p38 MAPK pathway but has little effect on some colonizers and the makeup of microbiotas with higher richness.…”

Section: Related To Gut Microbiotamentioning

confidence: 99%

Protective Application of Chinese Herbal Compounds and Formulae in Intestinal Inflammation in Humans and Animals

Yang,

Xiao,

Cheng

et al. 2023

Molecules

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Intestinal inflammation is a chronic gastrointestinal disorder with uncertain pathophysiology and causation that has significantly impacted both the physical and mental health of both people and animals. An increasing body of research has demonstrated the critical role of cellular signaling pathways in initiating and managing intestinal inflammation. This review focuses on the interactions of three cellular signaling pathways (TLR4/NF-κB, PI3K-AKT, MAPKs) with immunity and gut microbiota to explain the possible pathogenesis of intestinal inflammation. Traditional medicinal drugs frequently have drawbacks and negative side effects. This paper also summarizes the pharmacological mechanism and application of Chinese herbal compounds (Berberine, Sanguinarine, Astragalus polysaccharide, Curcumin, and Cannabinoids) and formulae (Wumei Wan, Gegen-Qinlian decoction, Banxia xiexin decoction) against intestinal inflammation. We show that the herbal compounds and formulae may influence the interactions among cell signaling pathways, immune function, and gut microbiota in humans and animals, exerting their immunomodulatory capacity and anti-inflammatory and antimicrobial effects. This demonstrates their strong potential to improve gut inflammation. We aim to promote herbal medicine and apply it to multispecies animals to achieve better health.

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Section: Related To Gut Microbiotamentioning

confidence: 99%

Protective Application of Chinese Herbal Compounds and Formulae in Intestinal Inflammation in Humans and Animals

Yang,

Xiao,

Cheng

et al. 2023

Molecules

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“…Despite its importance, the connection between these two functions is poorly understood. Recently it was shown in C. elegans that mutations in the genes involved in apoptotic cell clearance make them more resistant to the pathogenic bacteria Pseudomonas aeruginosa and Salmonella typhimurium [18]. The mutant worms showed an upregulation of the innate immune response genes, even in the absence of bacterial pathogens, and this response was actively regulated by the apoptotic cell clearance defects through the PMK-1 and MPK-1 pathways [18].…”

Section: The Interconnection Of Innate Immunity With Apoptotic Cell Clearance and The Nervous Systemmentioning

confidence: 99%

“…Finally, we summarize emerging data analyzing poorly understood interconnections between the two phagocytic functions, apoptotic clearance and initiation of the innate immune response against pathogens. Recent data obtained in both worms and mammals suggest activation of innate immunity as a consequence of defective apoptotic clearance [18].…”

Section: Introductionmentioning

confidence: 99%

Conserved and Distinct Elements of Phagocytosis in Human and C. elegans

Lukácsi

Farkas

Saskői

et al. 2021

IJMS

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Endocytosis provides the cellular nutrition and homeostasis of organisms, but pathogens often take advantage of this entry point to infect host cells. This is counteracted by phagocytosis that plays a key role in the protection against invading microbes both during the initial engulfment of pathogens and in the clearance of infected cells. Phagocytic cells balance two vital functions: preventing the accumulation of cell corpses to avoid pathological inflammation and autoimmunity, whilst maintaining host defence. In this review, we compare elements of phagocytosis in mammals and the nematode Caenorhabditis elegans. Initial recognition of infection requires different mechanisms. In mammals, pattern recognition receptors bind pathogens directly, whereas activation of the innate immune response in the nematode rather relies on the detection of cellular damage. In contrast, molecules involved in efferocytosis—the engulfment and elimination of dying cells and cell debris—are highly conserved between the two species. Therefore, C. elegans is a powerful model to research mechanisms of the phagocytic machinery. Finally, we show that both mammalian and worm studies help to understand how the two phagocytic functions are interconnected: emerging data suggest the activation of innate immunity as a consequence of defective apoptotic cell clearance.

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“…The MAPK pathways, such as PMK-1/p38 MAPK and MPK-1/ERK MAPK, play a major role in defensing against pathogens in C. elegans , and MAPK mutants are more sensitive to pathogens ( 21 , 22 ). Among the immune pathways, Insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) is conserved in various species.…”

Section: Introductionmentioning

confidence: 99%

Salmonella enterica serovar Paratyphi A-induced immune response in Caenorhabditis elegans depends on MAPK pathways and DAF-16

Ding

Zhang

et al. 2023

Front. Immunol.

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Salmonella enterica serovar Paratyphi A (S. Paratyphi A) is a pathogen that can cause enteric fever. According to the recent epidemic trends of typhoid fever, S. Paratyphi A has been the major important causative factor in paratyphoid fever. An effective vaccine for S. Paratyphi A has not been developed, which made it a tricky public health concern. Until now, how S. Paratyphi A interacts with organisms remain unknown. Here using lifespan assay, we found that S. Paratyphi A could infect Caenorhabditis elegans (C. elegans) at 25°C, and attenuate thermotolerance. The immune response of C. elegans was mediated by tir-1, nsy-1, sek-1, pmk-1, mpk-1, skn-1, daf-2 and daf-16, suggesting that S. Paratyphi A could regulate the MAPK and insulin pathways. Furthermore, we observed several phenotypical changes when C. elegans were fed S. Paratyphi A, including an accelerated decline in body movement, reduced the reproductive capacity, shortened spawning cycle, strong preference for OP50, arrested pharyngeal pumping and colonization of the intestinal lumen. The virulence of S. Paratyphi A requires living bacteria and is not mediated by secreting toxin. Using hydrogen peroxide analysis and quantitative RT-PCR, we discovered that S. Paratyphi A could increase oxidative stress and regulate the immune response in C. elegans. Our results sheds light on the infection mechanisms of S. Paratyphi A and lays a foundation for drugs and vaccine development.

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Defective apoptotic cell clearance activates innate immune response to protect Caenorhabditis elegans against pathogenic bacteria

Cited by 7 publications

References 44 publications

Protective Application of Chinese Herbal Compounds and Formulae in Intestinal Inflammation in Humans and Animals

Protective Application of Chinese Herbal Compounds and Formulae in Intestinal Inflammation in Humans and Animals

Conserved and Distinct Elements of Phagocytosis in Human and C. elegans

Salmonella enterica serovar Paratyphi A-induced immune response in Caenorhabditis elegans depends on MAPK pathways and DAF-16

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