AUTHOR=Wang Zhensheng , Zhai Wenya , Liu Hong 

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

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1447431

DOI=10.3389/fimmu.2024.1447431

ISSN=1664-3224

ABSTRACT=<p>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 (<italic>Megalobrama amblycephala</italic>). Despite its low sequence identity, it shares conserved structures and close evolutionary relationships with other teleost IL-22s. Furthermore, <italic>Aeromonas hydrophila</italic> (<italic>A. hydrophila</italic>) infection leads to tissue injury in <italic>M. amblycephala</italic> immune organs and concomitantly altered <italic>Mail-22</italic> 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 <italic>M. amblycephala</italic> post-<italic>A. hydrophila</italic> 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 <italic>A. hydrophila</italic>-induced activation of the ROS/NLRP3 inflammasome axis. Consistent with these findings, rMaIL-22 treatment attenuated the expression of proinflammatory cytokines (<italic>il-1β</italic>, <italic>tnf-α</italic> and <italic>il-6</italic>) and proapoptotic genes (<italic>caspase-3</italic> and <italic>caspase-8</italic>) while promoting antiapoptotic genes (<italic>bcl-2b</italic> and <italic>mcl-1a</italic>) 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.</p>