TLR22-mediated activation of TNF-α-caspase-1/IL-1β inflammatory axis leads to apoptosis of Aeromonas hydrophila-infected macrophages. (September 2021)

• Record Type: Journal Article
• Authors: Kumar, Manmohan; Kumar, Jai; Sharma, Shagun; Hussain, Md. Arafat; Shelly, Asha; Das, Bhabatosh; Yadav, Ajay Kumar; Mazumder, Shibnath
• Is Part Of: Molecular immunology. Volume 137(2021)
• Page Start: 114
• Page End: 123
• Publication Date: 2021-09
• Subjects: C. gariepinus Clarias gariepinus -- A. hydrophila Aeromonas hydrophila -- HK Headkidney -- HKM Headkidney macrophages -- TLR22 Toll-like receptor 22 -- TNF-α Tumour necrosis factor-α -- IL-1β Interleukin-1β; TLR22 -- Headkidney macrophage -- Apoptosis -- Caspase-1 -- TNF-α -- IL-1β; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2021.06.025
• Languages: English
• ISSNs: 0161-5890

Abstract

Graphical abstract: Highlights: TLR22 is expressed in immune and non-immune tissues of C. gariepinus. A. hydrophila infection incites TLR22 expression in HKM of C. gariepinus. TLR22 is critical in restraining intracellular replication of A. hydrophila. TLR22 induces TNF-α dependent activation of pro-inflammatory caspase-1/IL-1β axis. IL-1β contributes in caspase-3-mediated HKM apoptosis and A. hydrophila death. Abstract: Toll-like receptors (TLRs) represent first line of host defence against microbes. Amongst different TLRs, TLR22 is exclusively expressed in non-mammalian vertebrates, including fish. The precise role of TLR22 in fish-immunity remains abstruse. Herein, we used headkidney macrophages (HKM) from Clarias gariepinus and deciphered its role in fish-immunity. Highest tlr22 expression was observed in the immunocompetent organ – headkidney; nonetheless expression in other tissues suggests its possible involvement in non-immune sites also. Aeromonas hydrophila infection up-regulates tlr22 expression in HKM. Our RNAi based study suggested TLR22 restricts intracellular survival of A. hydrophila . Inhibitor and RNAi studies further implicated TLR22 induces pro-inflammatory cytokines TNF-α and IL-1β. We observed heightened caspase-1 activity and our results suggest the role of TLR22 in activating TNF-α/caspase-1/IL-1β cascade leading to caspase-3 mediated apoptosis of A. hydrophila -infected HKM. We conclude, TLR22 plays critical role in immune-surveillance and triggers pro-inflammatory cytokines leading to caspase mediated HKM apoptosis and pathogen clearance.