Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development

Abstract

How fish larvae are protected from infection before the maturation of adaptive immunity, a process which may take up to several weeks in most species, has long been a matter of speculation. Using a germfree model, we show that colonization by commensals in newly hatched zebrafish primes neutrophils and induces several genes encoding proinflammatory and antiviral mediators, increasing the resistance of larvae to viral infection. Commensal microbe recognition was found to be mediated mainly through a TLR/MyD88 signaling pathway, and professional phagocytes were identified as the source of these immune mediators. However, the induction of proinflammatory and antiviral genes, but not of antimicrobial effector genes, also required the covalent modification of histone H3 at gene promoters. Interestingly, chromatin modifications were not altered by commensal microbes or hatching. Taken together, our results demonstrate that gene-specific chromatin modifications are associated with the protection of zebrafish larvae against infectious agents before adaptive immunity has developed and prevent pathologies associated with excessive inflammation during development.epigenetic | cytokines | evolution | gene regulation | live imaging

Il-1β and Reactive Oxygen Species Differentially Regulate Neutrophil Directional Migration and Basal Random Motility in a Zebrafish Injury–Induced Inflammation Model

“…Although the assays are not done under germ-free conditions, they are carried out under relatively clean conditions by the use of sterilized egg water, solutions, and containers as well as rapid removal of dying embryos. Nonetheless, under these relatively clean conditions, the inflammatory response induced by injury is very similar to that under germ-free conditions: less il-1b production, fewer neutrophil infiltrations, and shorter proinflammation process compared with those under conventional conditions (56). We therefore believe our findings are likely to represent those under germ-free conditions.…”

TRPV4-Mediated Detection of Hyposmotic Stress by Skin Keratinocytes Activates Developmental Immunity

“…Myeloid cells respond to a set of exogenous microbes and endogenous danger-associated molecular patterns (DAMP), called microbial-associated molecular pattern (MAMP) and DAMP, respectively (4,5). Such molecules are recognized by diverse innate receptors, leading to the production of powerful messenger molecules, such as cytokines and eicosanoids (6,7). However, how vertebrates manage to mount a protective innate immune response before the definitive immune cellular components are fully developed remains an ongoing challenge (8)(9)(10)(11).…”

Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic trimer with new recognition and effector faces

“…In bony fish, pattern-recognition receptors (PRRs) of the innate immune system are divided into two families with vast recognition capacities: the transmembrane Toll-like receptors (TLRs) and intracytoplasmic Nod-like receptors, which are conserved in mammals (Galindo-Villegas et al, 2012). Other important PRRs are soluble serum short-chain pentraxins, which have been studied at both the gene (Falco et al, 2012) and protein levels (Cartwright et al, 2004;Huong Giang et al, 2010).…”