Journal Article

Megalobrama amblycephala IL-22 attenuates Aeromonas hydrophila induced inflammation, apoptosis and tissue injury by regulating the ROS/NLRP3 inflammasome axis

Liu, Hong, Wang, Zhensheng, Zhai, Wenya

2024

Overview

Mammalian interleukin-22 (IL-22) attenuates organismal injury by inhibiting reactive oxygen species (ROS) and impeding the NLRP3 inflammasome activation. However, the role of fish IL-22 in this process remains unclear. We characterized MaIL-22, an IL-22 homolog in blunt snout bream ( Megalobrama amblycephala ). Despite its low sequence identity, it shares conserved structures and close evolutionary relationships with other teleost IL-22s. Furthermore, Aeromonas hydrophila ( A. hydrophila ) infection leads to tissue injury in M. amblycephala immune organs and concomitantly altered Mail-22 mRNA expression, suggesting that MaIL-22 was involved in the antimicrobial immune response. To explore MaIL-22’s biological functions, we produced recombinant MaIL-22 (rMaIL-22) protein and demonstrated it significantly enhanced the survival of M. amblycephala post- A. hydrophila infection. To unravel its protective mechanisms, we explored the ROS/NLRP3 inflammasome axis and its downstream signaling responses. The results showed that rMaIL-22 treatment significantly elevated antioxidant enzyme (T-SOD, CAT and GSH-PX) activities to inhibit MDA activity and scavenge ROS in visceral tissues. Meanwhile, rMaIL-22 impeded the activation of NLRP3 inflammasome by suppressing NLRP3 protein and mRNA expression. This indicated that rMaIL-22 contributed to inhibit A. hydrophila -induced activation of the ROS/NLRP3 inflammasome axis. Consistent with these findings, rMaIL-22 treatment attenuated the expression of proinflammatory cytokines ( il-1β , tnf-α and il-6 ) and proapoptotic genes ( caspase-3 and caspase-8 ) while promoting antiapoptotic genes ( bcl-2b and mcl-1a ) expression, ultimately mitigating tissue injury in visceral tissues. In conclusion, our research underscores MaIL-22’s key role in microbial immune regulation, offering insights for developing IL-22-targeted therapies and breeding programs.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Aeromonas hydrophila / Aeromonas hydrophila - immunology / Amino acids / Animals / anti-inflammatory / antiapoptotic / antioxidant / Antioxidants / Apoptosis / Apoptosis - drug effects / Aquaculture / bacterial disease / Bacterial infections / Caspase-3 / Caspase-8 / Conserved sequence / Cyprinidae - immunology / Cyprinidae - metabolism / Fish / Fish Diseases - immunology / Fish Diseases - microbiology / Fish Proteins - genetics / Fish Proteins - immunology / Fish Proteins - metabolism / Gene expression / Genes / Gram-Negative Bacterial Infections - immunology / Homeostasis / Immune response / Immune system / Immunology / Immunoregulation / Inflammasomes / Inflammasomes - immunology / Inflammasomes - metabolism / Inflammation / Inflammation - immunology / Interleukin 22 / Interleukins - immunology / Interleukins - metabolism / Laboratory animals / Megalobrama amblycephala / NLR Family, Pyrin Domain-Containing 3 Protein - metabolism / Phylogenetics / Proteins / Reactive oxygen species / Reactive Oxygen Species - metabolism / Signal Transduction