Inflammasomes in Teleosts: Structures and Mechanisms That Induce Pyroptosis during Bacterial Infection

Abstract

Pattern recognition receptors (PRRs) play a crucial role in inducing inflammatory responses; they recognize pathogen-associated molecular patterns, damage-associated molecular patterns, and environmental factors. Nucleotide-binding oligomerization domain-leucine-rich repeat-containing receptors (NLRs) are part of the PRR family; they form a large multiple-protein complex called the inflammasome in the cytosol. In mammals, the inflammasome consists of an NLR, used as a sensor molecule, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) as an adaptor protein, and pro-caspase1 (Casp1). Inflammasome activation induces Casp1 activation, promoting the maturation of proinflammatory cytokines, such as interleukin (IL)-1β and IL-18, and the induction of inflammatory cell death called pyroptosis via gasdermin D cleavage in mammals. Inflammasome activation and pyroptosis in mammals play important roles in protecting the host from pathogen infection. Recently, numerous inflammasome-related genes in teleosts have been identified, and their conservation and/or differentiation between their expression in mammals and teleosts have also been elucidated. In this review, we summarize the current knowledge of the molecular structure and machinery of the inflammasomes and the ASC-spec to induce pyroptosis; moreover, we explore the protective role of the inflammasome against pathogenic infection in teleosts.

Effects of functional polysaccharide from silkworm as an immunostimulant on transcriptional profiling and disease resistance in fish

“…Generally, inflammatory responses are tightly regulated by the interaction between cytokine components; the activation of inflammatory responses is aimed at enhancing the antimicrobial capacity of immune cells, facilitating pathogen clearance, and assisting tissue repair mechanisms (Grayfer and Belosevic, 2012;Morimoto et al, 2021). In the current study, we found various cytokines and their putative receptors were significantly affected in the liver of medaka fed with dietary silkrose-BM.…”

New insights into the evolutionary dynamic and lineage divergence of gasdermin E in metazoa

“…In human, caspase-1/4/5/8 and neutrophil elastase cleave GSDMD, while caspase-3 cleaves GSDME, and all these cleavages occur in the inter-domain linker region (Kayagaki et al, 2015;Shi et al, 2015;Rogers et al, 2017;Wang et al, 2017;Kambara et al, 2018;Orning et al, 2018). In contrast, different cleavage modes exist in the lower vertebrate teleost, which comprise more than half of all living vertebrate species and possess only GSDME and GSDMF (Hofmann, 2020;Morimoto et al, 2021). In zebrafish Danio rerio, two GSDME orthologs, designated GSDMEa and GSDMEb, are cleaved by caspase-3 and caspy2 (caspase-4/5 homolog), respectively, to induce pyroptosis (Li et al, 2020;Wang et al, 2020), while in tongue sole Cynoglossus semilaevis, GSDME-mediated pyroptosis is activated by caspase-1/3/7 (Jiang et al, 2019).…”

A new pyroptosis model can predict the immunotherapy response and immune microenvironment characteristics and prognosis of patients with cutaneous melanoma based on TCGA and GEO databases

“…When the body is invaded by pathogens, inflammatory caspase is activated, which eventually leads to the lysis of GSDMs. GSDM-NTs perforate the cell membrane surface, thereby inducing lytic death of pathogens and infected host cells (1,2,6,7).…”

“…Gasdermin D (GSDMD) was first discovered in 2015 and was identified as the key executive protein of downstream molecular signals after the activation of caspase (4,5). The classical pyroptosis pathway is mediated by the assembly of inflammasomes, including NLRC4, NLRP1, NLRP2, NLRP3, NLRP6, NLRP7, and AIM2 (6,7). Inflammasomes and their related cytokines are also associated with the tumor immune microenvironment and prognosis (8,9).…”