title: Toll-like receptor 10 is involved in induction of innate immune responses to influenza virus infection.
abstract: Toll-like receptors (TLRs) play key roles in innate immune recognition of pathogen-associated molecular patterns of invading microbes. Among the 10 TLR family members identified in humans, TLR10 remains an orphan receptor without known agonist or function. TLR10 is a pseudogene in mice and mouse models are noninformative in this regard. Using influenza virus infection in primary human peripheral blood monocyte-derived macrophages and a human monocytic cell line, we now provide previously unidentified evidence that TLR10 plays a role in innate immune responses following viral infection. Influenza virus infection increased TLR10 expression and TLR10 contributed to innate immune sensing of viral infection leading to cytokine induction, including proinflammatory cytokines and interferons. TLR10 induction is more pronounced following infection with highly pathogenic avian influenza H5N1 virus compared with a low pathogenic H1N1 virus. Induction of TLR10 by virus infection requires active virus replication and de novo protein synthesis. Culture supernatants of virus-infected cells modestly up-regulate TLR10 expression in nonvirus-infected cells. Signaling via TLR10 was activated by the functional RNA-protein complex of influenza virus leading to robust induction of cytokine expression. Taken together, our findings identify TLR10 as an important innate immune sensor of viral infection and its role in innate immune defense and immunopathology following viral and bacterial pathogens deserves attention.
authors.affiliation: University of Hong Kong-Pasteur Research Pole and Centre of Influenza Research, School of Public Health, State Key Laboratory of Emerging Infectious Diseases, and Department of Biochemistry, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Suki M Y
authors.initials: SM
authors.lastname: Lee
authors.forename: Kin-Hang
authors.initials: KH
authors.lastname: Kok
authors.forename: Martial
authors.initials: M
authors.lastname: Jaume
authors.forename: Timothy K W
authors.initials: TK
authors.lastname: Cheung
authors.forename: Tsz-Fung
authors.initials: TF
authors.lastname: Yip
authors.forename: Jimmy C C
authors.initials: JC
authors.lastname: Lai
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.forename: Robert G
authors.initials: RG
authors.lastname: Webster
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Jin
authors.forename: J S Malik
authors.initials: JS
authors.lastname: Peiris
mesh_terms: D000818:Animals; D052160:Benzothiazoles; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D003959:Diamines; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008264:Macrophages; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D009930:Organic Chemicals; D011804:Quinolines; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051201:Toll-Like Receptor 10 / Q000276:immunology* / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; D017931:DNA Primers; D003959:Diamines; D009930:Organic Chemicals; D011804:Quinolines; D034741:RNA, Small Interfering; D051201:Toll-Like Receptor 10; C098022:SYBR Green I