PMID- 19555720 OWN - NLM STAT- MEDLINE DCOM- 20091217 LR - 20220330 IS - 1879-0542 (Electronic) IS - 0165-2478 (Print) IS - 0165-2478 (Linking) VI - 125 IP - 2 DP - 2009 Aug 15 TI - TLR5 ligation by flagellin converts tolerogenic dendritic cells into activating antigen-presenting cells that preferentially induce T-helper 1 responses. PG - 114-8 LID - 10.1016/j.imlet.2009.06.007 [doi] AB - Dendritic cells (DCs) differentiated in the presence of IL-10 preferentially induce regulatory T-cells and tolerance. Whether the tolerogenic properties displayed by these DCs (Tol-DCs) can be overcome has not been fully explored. Here we show for the first time that Tol-DCs express higher levels of TLR5 mRNA, but not TLR4 or TLR9 mRNA relative to DCs differentiated with GM-CSF and IL-4 (BM-DCs). In response to flagellin, a natural TLR-5 ligand, Tol-DCs produced IL-12 but not IL-10. Unlike Tol-DCs stimulated with LPS, which produce high levels of IL-10 and fail to generate a cognate inflammatory response in CD4(+) T-cells, flagellin-stimulated Tol-DCs promoted the differentiation of CD4(+) T cells with a T-helper 1 phenotype. The divergent T-cell outcomes induced by Tol-DCs in response to different TLR-ligands highlights not only their plasticity, but also points to TLR5 ligation as a potential strategy to overcome tolerance in environments that are otherwise conducive to immune unresponsiveness. FAU - Vicente-Suarez, Ildelfonso AU - Vicente-Suarez I AD - Division of Immunology and Division of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, United States. FAU - Brayer, Jason AU - Brayer J FAU - Villagra, Alejandro AU - Villagra A FAU - Cheng, Fengdong AU - Cheng F FAU - Sotomayor, Eduardo M AU - Sotomayor EM LA - eng GR - R01 CA087583/CA/NCI NIH HHS/United States GR - CA87583/CA/NCI NIH HHS/United States GR - R01 CA100850/CA/NCI NIH HHS/United States GR - CA100850/CA/NCI NIH HHS/United States GR - R01 CA087583-09/CA/NCI NIH HHS/United States GR - R01 CA100850-05/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090623 PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (Toll-Like Receptor 5) RN - 12777-81-0 (Flagellin) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - *Antigen Presentation/drug effects MH - Bone Marrow Cells/immunology MH - Cell Differentiation/drug effects/immunology MH - Dendritic Cells/drug effects/*immunology/metabolism MH - Flagellin/pharmacology MH - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism MH - Interferon-gamma/*metabolism MH - Interleukin-10/metabolism MH - Interleukin-12/*metabolism MH - Interleukin-4/metabolism MH - Lymphocyte Activation/drug effects MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Transgenic MH - Protein Binding MH - Receptors, Antigen, T-Cell MH - Th1 Cells/immunology/*metabolism/pathology MH - Toll-Like Receptor 5/genetics/immunology/*metabolism PMC - PMC2758552 MID - NIHMS127332 EDAT- 2009/06/27 09:00 MHDA- 2009/12/18 06:00 PMCR- 2010/08/15 CRDT- 2009/06/27 09:00 PHST- 2009/02/17 00:00 [received] PHST- 2009/06/12 00:00 [revised] PHST- 2009/06/15 00:00 [accepted] PHST- 2009/06/27 09:00 [entrez] PHST- 2009/06/27 09:00 [pubmed] PHST- 2009/12/18 06:00 [medline] PHST- 2010/08/15 00:00 [pmc-release] AID - S0165-2478(09)00163-1 [pii] AID - 10.1016/j.imlet.2009.06.007 [doi] PST - ppublish SO - Immunol Lett. 2009 Aug 15;125(2):114-8. doi: 10.1016/j.imlet.2009.06.007. Epub 2009 Jun 23.