Bacterial flagellin inhibits T cell receptor-mediated activation of T cells by inducing suppressor of cytokine signalling-1 (SOCS-1).
Flagellin, the structural component of bacterial flagella, is secreted by pathogenic and commensal bacteria, and is recognized by Toll-like receptor (TLR) 5. Flagellin is a common bacterial antigen present on most motile bacteria and is speculated to contribute to the activation of CD4+ T cells in the intestine. However, molecular mechanisms by which flagellin regulate T cell activation remains to be determined. Using Jurkat T cells or human primary T cell, we showed that flagellin stimulation induced tyrosine phosphorylation of TLR5 and activation of both mitogen-activated protein kinases and nuclear factor kappaB. In addition, stimulation by flagellin did not induce nuclear factor of activated T cells (NFAT) activation, while stimulation via the T cell receptor (TCR) leads to activation of NFAT. However, TCR-mediated NFAT activation and tyrosine phosphorylation of zeta-associated protein 70 (Zap-70) were inhibited in cells pre-stimulated by flagellin. Furthermore, flagellin stimulation induced suppressor of cytokine signalling-1 (SOCS-1), which formed a complex with Zap-70 after stimulation via TCR, and inhibition of SOCS-1 expression by SOCS-1-specific small interfering RNA reinstated TCR-mediated activation of NFAT in cells pre-stimulated with flagellin. These results collectively indicate that bacterial flagellin inhibits TCR-mediated activation of T cells by inducing SOCS-1.
Okugawa
Shu
S
Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yanagimoto
Shintaro
S
Tsukada
Kunihisa
K
Kitazawa
Takatoshi
T
Koike
Kazuhiko
K
Kimura
Satoshi
S
Nagase
Hiroyuki
H
Hirai
Koich
K
Ota
Yasuo
Y
D015153:Blotting, Western; D004789:Enzyme Activation; D005408:Flagellin / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000276:immunology; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012475:Salmonella / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000276:immunology
D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D005408:Flagellin; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D020928:Mitogen-Activated Protein Kinases