Chicken miR-126-5p negatively regulates antiviral innate immunity by targeting TRAF3

Autor: Jie Wang, Yuqiang Cheng, Longlong Wang, Aixi Sun, Zhenyu Lin, Wenxian Zhu, Zhaofei Wang, Jingjiao Ma, Henan Wang, Yaxian Yan, Jianhe Sun
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Veterinary Research, Vol 53, Iss 1, Pp 1-14 (2022)
Druh dokumentu: article
ISSN: 1297-9716
DOI: 10.1186/s13567-022-01098-x
Popis: Abstract Innate immunity plays an essential role in preventing the invasion of pathogenic microorganisms. However, innate immunity is a double-edged sword, whose excessive activation is detrimental to immune homeostasis and even leads to a “cytokine storm” of the infected host. The host develops a series of negative regulatory mechanisms to balance the immune response. Here, we report a negative regulatory mechanism of chicken innate immunity mediated by miRNA. In the GEO database, we found that miR-126-5p was markedly up-regulated in chickens infected by RNA viruses. Upregulation of miR-126-5p by RNA virus was then further shown via both a cell model and in vivo tests. Overexpression of miR-126-5p significantly inhibited the expression of interferon and inflammatory cytokine-related genes induced by RNA viruses. The opposite result was achieved after the knockdown of miR-126-5p expression. Bioinformatics analysis identified TRAF3 as candidate target gene of miR-126-5p. Experimentally, miR-126-5p can target TRAF3, as shown by the effects of miR-126-5p on the endogenous expression of TRAF3, and by the TRAF3 3'UTR driven luciferase reporter assay. Furthermore, we demonstrated that miR-126-5p negatively regulated innate immunity by blocking the MAVS-TRAF3-TBK1 axis, with a co-expression assay. Overall, our results suggest that miR-126-5p is involved in the negative regulation of chicken innate immunity, which might contribute to maintaining immune balance.
Databáze: Directory of Open Access Journals