Toll-like receptor 2 controls expansion and function of regulatory T cells
| Autor: | Shizuo Akira, Martijn H. den Brok, Roger P.M. Sutmuller, Erik Bennink, Leo A. B. Joosten, Gosse J. Adema, Matthijs Kramer, Bart Jan Kullberg, Mihai G. Netea, Liza W.J. Toonen |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Lipoproteins
T cell Receptors Antigen T-Cell Antigen-Presenting Cells chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Auto-immunity transplantation and immunotherapy [N4i 4] Invasive mycoses and compromised host [N4i 2] Mice Immune system Immune Regulation [NCMLS 2] Translational research [ONCOL 3] Effective Primary Care and Public Health [EBP 3] medicine Perception and Action [DCN 1] Animals Cysteine Transgenes Antigen-presenting cell Adaptor Proteins Signal Transducing Mice Knockout Chronic inflammation and autoimmunity [UMCN 4.2] Toll-like receptor Innate immune system Candidiasis TLR9 Receptors Interleukin-2 hemic and immune systems General Medicine Toll-Like Receptor 2 Mice Inbred C57BL Pathogenesis and modulation of inflammation [N4i 1] TLR2 medicine.anatomical_structure CD4 Antigens Myeloid Differentiation Factor 88 Immunology TLR4 Microbial pathogenesis and host defense [UMCN 4.1] Infection and autoimmunity [NCMLS 1] Research Article Signal Transduction Immunity infection and tissue repair [NCMLS 1] |
| Zdroj: | Journal of Clinical Investigation, 116, 485-94 Journal of Clinical Investigation, 116, 2, pp. 485-94 |
| ISSN: | 0021-9738 |
| Popis: | Contains fulltext : 51072.pdf ( ) (Closed access) Tregs play a central role in the suppression of immune reactions and prevention of autoimmune responses harmful to the host. During acute infection, however, Tregs might hinder effector T cell activity directed toward the elimination of the pathogenic challenge. Pathogen recognition receptors from the TLR family expressed by innate immune cells are crucial for the generation of effective immunity. We have recently shown the CD4CD25 Treg subset in TLR2 mice to be significantly reduced in number compared with WT littermate control mice, indicating a link between Tregs and TLR2. Here, we report that the TLR2 ligand Pam3Cys, but not LPS (TLR4) or CpG (TLR9), directly acts on purified Tregs in a MyD88-dependent fashion. Moreover, when combined with TCR stimulation, TLR2 triggering augmented Treg proliferation in vitro and in vivo and resulted in a temporal loss of the suppressive Treg phenotype in vitro by directly affecting Tregs. Importantly, WT Tregs adoptively transferred into TLR2 mice were neutralized by systemic administration of TLR2 ligand during the acute phase of a Candida albicans infection, resulting in a 100-fold reduced C. albicans outgrowth. This demonstrates that in vivo TLR2 also controls the function of Tregs and establishes a direct link between TLRs and the control of immune responses through Tregs. |
| Databáze: | OpenAIRE |
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