Butyrate-induced IL-22 expression in fish macrophages contributes to bacterial clearance

Jinjin Zhang, Wentao Wang, Shufei Liang, Rui Shao, Wenkai Shi, Gudmundur H. Gudmundsson, Peter Bergman, Qinghui Ai, Kangsen Mai, Min Wan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


IL-22 has been characterized as a critical cytokine in maintaining barrier integrity and host immunity. So far, it has been known that IL-22 is mainly produced by lymphoid lineage cells. In the present study, we have thoroughly investigated butyrate-induced production and function of IL-22 in fish macrophages. Our results demonstrated that short-chain fatty acids (SCFAs), major microbiota-derived metabolites, promoted the expression of IL-22 in head kidney macrophages (HKMs) of turbot (Scophthalmus maximus L.). Interestingly, butyrate-mediated intracellular bacterial killing in HKMs diminished when IL-22 expression was interfered. Furthermore, the turbot fed the diet containing sodium butyrate (NaB) exhibited significantly lower mortality after bacterial infection, compared to the fish fed a basal diet. At the meantime, a higher level of IL-22 expression and bactericidal activity was detected in HKMs from the turbot fed NaB-supplemented diet. In addition, NaB treatment promoted the expression of antimicrobial peptides (AMPs) β-defensins in zebrafish (Danio rerio). However, butyrate-induced expression of AMPs was reduced in IL-22 mutant zebrafish compared to wild-type (WT) fish. Meanwhile, NaB treatment was incapable to protect IL-22 mutant fish from bacterial infection as it did in WT zebrafish. Importantly, our results demonstrated that IL-22 expression was remarkably suppressed in macrophage-depleted zebrafish, indicating that macrophage might be a cell source of IL-22 production in vivo. In conclusion, all these findings collectively revealed that SCFAs regulated the production and function of IL-22 in fish macrophages, which facilitated host resistance to bacterial invasion.

Original languageEnglish
Article number108545
JournalFish and Shellfish Immunology
Publication statusPublished - Feb 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Ltd

Other keywords

  • Antimicrobial peptides
  • IL-22
  • Infection
  • Macrophage
  • Short-chain fatty acids (SCFAs)


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