Recognition of double-stranded RNA by TLR3 induces severe small intestinal injury in mice.
The role of TLRs on intestinal epithelial cells (IECs) is controversial, and the mechanisms by which TLRs influence mucosal homeostasis are obscure. In this study, we report that genomic dsRNA from rotavirus, and its synthetic analog polyinosinic-polycytidylic acid (poly(I:C)), induce severe mucosal injury in the small intestine. Upon engaging TLR3 on IECs, dsRNA triggers IECs to secrete IL-15, which functions to increase the percentage of CD3+NK1.1+ intestinal intraepithelial lymphocytes (IELs) and enhances the cytotoxicity of IELs. Moreover, The CD3+NK1.1+ IELs are proved as CD8alphaalpha+ IELs. These results provide direct evidence that abnormal TLR3 signaling contributes to breaking down mucosal homeostasis and the first evidence of pathogenic effects mediated by CD8alphaalpha+ IELs. The data also suggest that genomic dsRNA may be involved in the pathogenesis of acute rotavirus gastroenteritis.
Zhou
Rongbin
R
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, 443 Huang-shan Road, Hefei, China.
Wei
Haiming
H
Sun
Rui
R
Tian
Zhigang
Z
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D005759:Gastroenteritis / Q000276:immunology / Q000473:pathology* / Q000821:virology; D019409:Interleukin-15 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology* / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000276:immunology; D012330:RNA, Double-Stranded / Q000276:immunology*; D012367:RNA, Viral / Q000276:immunology*; D012401:Rotavirus; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology*
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D019409:Interleukin-15; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D051196:Toll-Like Receptor 3; D011070:Poly I-C