Galindo-Villegas, J., García-Moreno, D., de Oliveira, S., Meseguer, J., and Mulero, V. (2012) Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development. Proceedings of the National Academy of Sciences of the United States of America. 109(39):E2605-2614.
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 germ-free 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.