PMID- 27616282 OWN - NLM STAT- MEDLINE DCOM- 20170308 LR - 20170308 IS - 1618-0607 (Electronic) IS - 1438-4221 (Linking) VI - 306 IP - 8 DP - 2016 Dec TI - Staphylococcus aureus PSM peptides induce tolerogenic dendritic cells upon treatment with ligands of extracellular and intracellular TLRs. PG - 666-674 LID - S1438-4221(16)30242-9 [pii] LID - 10.1016/j.ijmm.2016.09.002 [doi] AB - Dendritic cells (DCs) are key players of the immune system and thus a target for immune evasion by pathogens. We recently showed that the virulence factor phenol-soluble modulin (PSM) produced by community-associated methicillin-resistant Staphylococcus aureus strains induces tolerogenic DCs upon Toll-like receptor (TLR) 2 activation via the p38-CREB-IL-10 pathway. Here, we addressed the question whether this tolerogenic phenotype of DCs induced by PSMs is specific for TLR2 activation. Therefore, bone marrow-derived DCs were treated with various ligands for extracellular and intracellular TLRs simultaneously with PSMalpha3. We show that PSMalpha3 modulates antigen uptake, maturation and cytokine production of DCs activated by TLR1/2, TLR2/6, TLR4, TLR7, and TLR9. Pre-incubation of DCs with a p38 MAP kinase inhibitor prevented the PSMalpha3-induced IL-10 secretion, as well as MHC class II up-regulation upon TLR activation. In consequence, the tolerogenic DCs induced by PSMalpha3 in response to several TLR ligands promoted priming of regulatory T cells. Thus, PSMs could be useful as inducers of tolerogenic DCs upon TLR ligand stimulation for therapeutic applications. CI - Copyright A(c) 2016 Elsevier GmbH. All rights reserved. FAU - Armbruster, Nicole S AU - Armbruster NS AD - Department of Internal Medicine II, University of Tubingen, Tubingen, Germany. FAU - Richardson, Jennifer R AU - Richardson JR AD - Department of Internal Medicine II, University of Tubingen, Tubingen, Germany. FAU - Schreiner, Jens AU - Schreiner J AD - Institute for Cell Biology, University of Tubingen, Tubingen, Germany. FAU - Klenk, Juliane AU - Klenk J AD - Department of Internal Medicine II, University of Tubingen, Tubingen, Germany. FAU - Gunter, Manina AU - Gunter M AD - Department of Internal Medicine II, University of Tubingen, Tubingen, Germany. FAU - Autenrieth, Stella E AU - Autenrieth SE AD - Department of Internal Medicine II, University of Tubingen, Tubingen, Germany. Electronic address: Stella.Autenrieth@med.uni-tuebingen.de. LA - eng PT - Journal Article DEP - 20160903 PL - Germany TA - Int J Med Microbiol JT - International journal of medical microbiology : IJMM JID - 100898849 RN - 0 (Antigens, Bacterial) RN - 0 (Bacterial Toxins) RN - 0 (Toll-Like Receptors) RN - 0 (staphylococcal delta toxin) SB - IM MH - Animals MH - Antigens, Bacterial/*immunology MH - Bacterial Toxins/*immunology MH - Dendritic Cells/*immunology MH - Female MH - *Immune Tolerance MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Staphylococcus aureus/*immunology MH - T-Lymphocytes, Regulatory/*immunology MH - Toll-Like Receptors/*metabolism OTO - NOTNLM OT - IL-10 OT - PSM OT - Staphylococcus aureus OT - TLR OT - Tolerogenic DC OT - p38 EDAT- 2016/09/13 06:00 MHDA- 2017/03/09 06:00 CRDT- 2016/09/13 06:00 PHST- 2016/04/20 00:00 [received] PHST- 2016/08/23 00:00 [revised] PHST- 2016/09/01 00:00 [accepted] PHST- 2016/09/13 06:00 [pubmed] PHST- 2017/03/09 06:00 [medline] PHST- 2016/09/13 06:00 [entrez] AID - S1438-4221(16)30242-9 [pii] AID - 10.1016/j.ijmm.2016.09.002 [doi] PST - ppublish SO - Int J Med Microbiol. 2016 Dec;306(8):666-674. doi: 10.1016/j.ijmm.2016.09.002. Epub 2016 Sep 3.