GPCR Signaling in C. elegans and Its Implications in Immune Response

Gupta, Akash; Singh, Varsha

doi:10.1016/bs.ai.2017.05.002

Cited by 16 publications

(7 citation statements)

References 51 publications

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“…Pioneering work by the Ausubel group was rapidly expanded to include many bacterial and fungal species of interest to humans (Aballay and Ausubel, 2002;Kim et al, 2002;Labrousse et al, 2000;Mallo et al, 2002;Pukkila-Worley et al, 2011). Detailed reviews have been written about many of the pathways involved and their conservation in mammals, including the importance of the MAPK pathways during infection (Kim and Ewbank, 2018), the roles played by autophagy during immunity (Kuo et al, 2018), and GPCR signalling in infection (Gupta and Singh, 2017;Reboul and Ewbank, 2016). Several important areas lack recent summaries or have seen considerable recent developments, and those will be the focus here.…”

Section: Monitoring Damage and Infection Of The Intestinementioning

confidence: 99%

“…Neuro-immune communication involves several neuronal circuits, neurotransmitters and neuropeptides, G-protein-coupled receptors (GPCRs) and their ligands, transforming growth factor-β ligands, and insulin signalling. These pathways have been extensively reviewed (Gupta and Singh, 2017;Reboul and Ewbank, 2016;Singh and Aballay, 2020;Wani et al, 2020). Other non-neuronal tissue communication mechanisms involved in maintaining the whole organism homeostasis have started to be revealed (Figure 3).…”

Section: Cell Non-autonomous Responsementioning

confidence: 99%

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Innate immunity in C. elegans

Martineau

Kirienko

Pujol

2021

Current Topics in Developmental Biology

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In its natural habitat, C. elegans encounters a wide variety of microbes, including food, commensals and pathogens. To be able to survive long enough to reproduce, C. elegans has developed a complex array of responses to pathogens. These activities are coordinated on scales that range from individual organelles to the entire organism. Often, the response is triggered within cells, by detection of infection-induced damage, mainly in the intestine or epidermis. C. elegans has, however, a capacity for cell non-autonomous regulation of these responses. This frequently involves the nervous system, integrating pathogen recognition, altering host biology and governing avoidance behaviour. Although there are significant differences with the immune system of mammals, some mechanisms used to limit pathogenesis show remarkable phylogenetic conservation. The past twenty years have witnessed an explosion of host-pathogen interaction studies using C. elegans as a model. This review will discuss the broad themes that have emerged and highlight areas that remain to be fully explored. Natural environment and microbiotaCaenorhabditis elegans is a small free-living nematode found worldwide, predominately in humid, temperate areas where it can feed on the bacteria that proliferate on decaying vegetation (Schulenburg and Félix, 2017). Its natural environment comprises a complex community of microbes, including bacteria, fungi and viruses, including many parasitic species. The effect of environmental microbes on worm fitness can be beneficial, detrimental or mixed (Khan et al., 2018). And as the same microorganism can sometime be either beneficial or detrimental depending on the environmental conditions or the genotype of the host (Gravato-Nobre et al., 2020;Zarate-Potes et al., 2020), we will use the terms of "pathogen" or "commensal" for a given microbe as a simplification.A broad range of microorganisms can infect nematodes in a variety of ways. Different fungi, for example, have independently acquired the capacity to infect worms using diverse strategies (Lebrigand et al., 2016). Some species capture their prey with adhesive structure such as Arthobotrys oligosora or elegant mechanical traps like the constricting rings of al., 2001). Apart from recognition of viral replication products by DRH-1/RIG-1 (Ashe et al., 2013), see below, examples of direct microbial detection that lead to immune pathway activation remain elusive in C. elegans (Kim and Ewbank, 2018).Various molecules from the host, such as the protein HMGB1, formylated peptides, mitochondrial DNA, or uric acid, amongst many others, can also trigger innate immune activity (Tang et al., 2012). Matzinger and colleagues recognized that cells are agnostic with regard to the origin of the damage signals and will respond to them regardless of the preceding event, which led to the 'damage-associated molecular pattern' or DAMP hypothesis (Matzinger, 2002;Seong and Matzinger, 2004). On this basis, the field of innate immunity widened to include recognition of both non-self and se...

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Section: Monitoring Damage and Infection Of The Intestinementioning

confidence: 99%

Section: Cell Non-autonomous Responsementioning

confidence: 99%

Innate immunity in C. elegans

Martineau

Kirienko

Pujol

2021

Current Topics in Developmental Biology

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“…G protein-coupled receptors (GPCRs), located in the plasma membrane, are the most representative and widespread superfamily of receptor proteins in all representatives of multicellular eukaryotes. GPCRs have been found in fungi [1,2], plants [3], and in all studied invertebrates and vertebrates [4][5][6][7]. Prototypes of the structural domains of both GPCRs and the adapter and regulatory proteins that interact with them appeared at the earliest stages of evolution, already at the level of prokaryotes and unicellular eukaryotes [2,8,9].…”

Section: Introductionmentioning

confidence: 99%

Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands

Ao¹

2023

Preprint

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A separate group consists of compounds that are able to simultaneously interact with both orthosteric and allosteric sites, which are classified as bitopic GPCR ligands [74, 76-81]. They have two pharmacophores, one of which binds with high affinity to the orthosteric site, while the other, with lower affinity, binds to the allosteric site. If these sites are spatially separated in the receptor, then the pharmacophores in the bitopic ligand must be connected with a flexible linker, the length of which exactly corresponds to the distance between the orthosteric and allosteric sites. At the same time, it is important that the linker does not significantly affect the conformational rearrangements in the receptor caused by its activation by orthosteric and (or) allosteric agonists [74, 79].

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“…In general, most of E. coli is efficiently disrupted by a muscular grinder in the pharynx of the worm. However, very few intact bacteria may escape from this defense system, and enter in the lumen of the worm intestine (Gupta & Singh 2017). The intestinal lumen of worms is frequently distended during aging, which accompanied by bacterial proliferation (Garigan et al 2002;McGee et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Indole produced during dysbiosis mediates host–microorganism chemical communication

Yang

Chen

et al. 2022

Preprint

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An imbalance of the gut microbiota, termed dysbiosis, has a substantial impact on host physiology. However, the mechanism by which host deals with gut dysbiosis to maintain fitness remains largely unknown. In C. elegans, E. coli, which is its bacterial diets, proliferates in its intestinal lumen during aging. Here, we demonstrate that progressive intestinal proliferation of E. coli activates the transcription factor DAF-16, which is required for maintenance of longevity and organismal fitness in worms with age. DAF-16 up-regulates two lysozymes lys-7 and lys-8, thus limiting the bacterial accumulation in the gut of worms during aging. During dysbiosis, the levels of indole produced by E. coli are increased in worms. Indole is involved in the activation of DAF-16 by TRPA-1 in neurons of worms. Our finding demonstrates that indole functions as a microbial signal of gut dysbiosis to promote fitness of the host.

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GPCR Signaling in C. elegans and Its Implications in Immune Response

Cited by 16 publications

References 51 publications

Innate immunity in C. elegans

Innate immunity in C. elegans

Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands

Indole produced during dysbiosis mediates host–microorganism chemical communication

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