Thoroughly Remold the Localization and Signaling Pathway of TLR22

Abstract

TLR22 exists in nearly all the poikilothermic vertebrates and plays a central role in the initiation of innate immunity and activation of adaptive immunity. TLR22 signaling pathway has been characterized in detail in fugu (Takifugu rubripes). Here, we thoroughly remold the localization and signaling pathways of TLR22. We characterized TLR22a and TLR22b in grass carp (Ctenopharyngodon idella), designated as CiTLR22a and CiTLR22b, and explored the ligand(s), adaptor(s), and signaling pathway(s). Results show that both CiTLR22a and CiTLR22b localize to lysosome, acidic compartment. Correspondingly, CiTLR22a and CiTLR22b directly bind and respond to dsRNA analog poly(I:C) at pH 5, but not at pH 7.4, the physiological pH. Moreover, CiTLR22a and CiTLR22b exhibit antagonistic function in signal transmission, wherein CiTLR22a facilitates the protein and phosphorylation levels of IRF7 and enhances the promoter activities of major IFNs and NF-κBs, while CiTLR22b downregulates IRF7 phosphorylation and IRF3 protein level and suppresses the IFN and NF-κB pathways. Further investigations revealed that CiTLR22a restrains grass carp reovirus (GCRV) replication and protects cells from GCRV infection, whereas CiTLR22b plays a negative role in response to GCRV infection. This is the first time to systematically clarify the signaling pathways of two isotype TLR22s; especially, subcellular localization and adaptor are different from previous TLR22 report, which results from technical limitations. The results will serve the antiviral immune mechanisms in poikilothermic vertebrates and evolutionary immunology.

Cyprinid‐specific duplicated membrane TLR5 senses dsRNA as functional homodimeric receptors

“…Zebrafish carries two membrane TLR5 and two CpG DNA receptors, TLR9 and TLR21 (Yeh et al , 2013; Voogdt et al , 2018). Grass carp ( Ctenopharyngodon idella ) possesses two TLR22 members (Ji et al , 2020) and tandem duplication TLR5 (similar to zebrafish: CiTLR5a and CiTLR5b) (Liao et al , 2017). However, the functions and mechanisms of these duplicated receptors remain largely unknown.…”

Grass Carp (Ctenopharyngodon idella) KAT8 Inhibits IFN 1 Response Through Acetylating IRF3/IRF7

“…IRF3 and IRF7 are the main transcription factors involved in IFN 1 production (43,44). It is known that phosphorylation is linked to the activated formation of IRF3 and IRF7 (45)(46)(47). However, grass carp KAT8 did not affect the phosphorylation level of IRF3 and IRF7 (Figure S1).…”

Transcriptome Annotation Reveals Minimal Immunogenetic Diversity Among Wyoming Toads, Anaxyrus Baxteri

“…TLR7 is known to bind single stranded RNA and TLR9 recognizes unmethylated CpG DNA sequences (Akira and Takeda 2004;Vidya et al 2018). TLR22 has been described from amphibians and teleost shes and studies with teleost TLR22 suggest it recognizes microbial RNA (Samanta et al 2014;Ji et al 2019;Du et al 2019). Further studies of anuran TLR function are needed to better characterize the implications of these gene losses for the Wyoming Toads.…”