title: Rapid CD4+ T-cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9.
abstract: Toll-like receptors (TLRs) can recognize microbial patterns and utilize adaptor molecules, such as-MyD88 or (TRIF TIR-domain-containing adapter-inducing interferon-β), to initiate downstream signaling that ultimately affects the initiation of adaptive immunity. In addition to this inflammatory role, TLR5 expression on dendritic cells can favor antigen presentation of flagellin peptides and thus increase the sensitivity of flagellin-specific T-cell responses in vitro and in vivo. Here, we examined the role of alternative signaling pathways that might regulate flagellin antigen presentation in addition to MyD88. These studies suggest a requirement for spleen tyrosine kinase, a noncanonical TLR-signaling adaptor molecule, and its downstream molecule CARD9 in regulating the sensitivity of flagellin-specific CD4(+) T-cell responses in vitro and in vivo. Thus, a previously unappreciated signaling pathway plays an important role in regulating the dominance of flagellin-specific T-cell responses.
authors.affiliation: Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, University of California Davis, Davis, CA, USA.
authors.forename: Shaikh M
authors.initials: SM
authors.lastname: Atif
authors.forename: Seung-Joo
authors.initials: SJ
authors.lastname: Lee
authors.forename: Lin-Xi
authors.initials: LX
authors.lastname: Li
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Sara
authors.initials: S
authors.lastname: Gorjestani
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.forename: Edina
authors.initials: E
authors.lastname: Schweighoffer
authors.forename: Victor L J
authors.initials: VL
authors.lastname: Tybulewicz
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McSorley
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005408:Flagellin / Q000276:immunology / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000276:immunology
chemical_list: D053468:CARD Signaling Adaptor Proteins; C513280:Card9 protein, mouse; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D015375:Receptors, Interleukin-2; D051198:Toll-Like Receptor 5; D005408:Flagellin; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse
keywords: Bacterial infection; CARD9; CD4+ T cells; Syk; TLRs