AUTHOR=Yang Yuan Yuan , Zheng Si Yao , Fang Hong , Wu Xiao Man , Zhang Jie , Chang Ming Xian 

TITLE=Immunoprotective Effects of Two Histone H2A Variants in the Grass Carp Against Flavobacterium columnare Infection

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.939464

DOI=10.3389/fimmu.2022.939464

ISSN=1664-3224

ABSTRACT=<p>In teleost fish, the nucleotide polymorphisms of histone H2A significantly affect the resistance or susceptibility of zebrafish to <italic>Edwardsiella piscicida</italic> infection. Whether histone H2A variants can enhance the resistance of grass carp to <italic>Flavobacterium columnare</italic> infection remains unclear. Here, the effects of 7 previously obtained variants (gcH2A-1~gcH2A-7) and 5 novel histone H2A variants (gcH2A-11, gcH2A-13~gcH2A-16) in response to <italic>F. columnare</italic> infection were investigated. It was found that these histone H2A variants could be divided into type I and II. Among them, 5 histone H2A variants had no any effects on the <italic>F. columnare</italic> infection, however 7 histone H2A variants had antibacterial activity against <italic>F. columnare</italic> infection. The gcH2A-4 and gcH2A-11, whose antibacterial activity was the strongest in type I and II histone H2A variants respectively, were picked out for yeast expression. Transcriptome data for the samples from the intestines of grass carp immunized with the engineered <italic>Saccharomyces cerevisiae</italic> expressing PYD1, gcH2A-4 or gcH2A-11 revealed that 5 and 12 immune-related signaling pathways were significantly enriched by gcH2A-4 or gcH2A-11, respectively. For the engineered <italic>S. cerevisiae</italic> expressing gcH2A-4, NOD-like receptor and Toll-like receptor signaling pathways were enriched for up-regulated DEGs. Besides NOD-like receptor and Toll-like receptor signaling pathways, the engineered <italic>S. cerevisiae</italic> expressing gcH2A-11 also activated Cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway and C-type lectin receptor signaling pathway. Furthermore, grass carp were immunized with the engineered <italic>S. cerevisiae</italic> expressing PYD1, gcH2A-4 or gcH2A-11 for 1 month and challenged with <italic>F. columnare.</italic> These grass carp immunized with gcH2A-4 or gcH2A-11 showed lower mortality and fewer numbers of <italic>F. columnare</italic> than did the control group. All these results suggest that gcH2A-4 and gcH2A-11 play important roles in evoking the innate immune responses and enhancing disease resistance of grass carp against <italic>F. columnare</italic> infection.</p>