PMID- 25153703 OWN - NLM STAT- MEDLINE DCOM- 20150522 LR - 20231110 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 8 DP - 2014 TI - Involvement of Toll-like receptors on Helicobacter pylori-induced immunity. PG - e104804 LID - 10.1371/journal.pone.0104804 [doi] LID - e104804 AB - Dendritic cells (DCs) play a major role in the innate immune response since they recognize a broad repertoire of PAMPs mainly via Toll-like receptors (TLRs). During Helicobacter pylori (H. pylori) infection, TLRs have been shown to be important to control cytokine response particularly in murine DCs. In the present study we analyzed the effect of blocking TLRs on human DCs. Co-incubation of human DCs with H. pylori resulted in the release of the pro-inflammatory cytokines IL-12p70, IL-6 and IL-10. Release of IL-12p70 and IL-10 was predominantly influenced when TLR4 signaling was blocked by adding specific antibodies, suggesting a strong influence on subsequent T cell responses through TLR4 activation on DCs. Co-incubation of H. pylori-primed DC with allogeneic CD4+ T cells resulted in the production of IFN-gamma and IL-17A as well as the expression of Foxp3, validating a mixed Th1/Th17 and Treg response in vitro. Neutralization of TLR4 during H. pylori infection resulted in significantly decreased amounts of IL-17A and IFN-gamma and reduced levels of Foxp3-expressing and IL-10-secreting T cells. Our findings suggest that DC cytokine secretion induced upon TLR4-mediated recognition of H. pylori influences inflammatory and regulatory T cell responses, which might facilitate the chronic bacterial persistence. FAU - Kabisch, Romy AU - Kabisch R AD - Institut fur Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universitat Munchen, Munchen, Germany. FAU - Mejias-Luque, Raquel AU - Mejias-Luque R AD - Institut fur Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universitat Munchen, Munchen, Germany. FAU - Gerhard, Markus AU - Gerhard M AD - Institut fur Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universitat Munchen, Munchen, Germany. FAU - Prinz, Christian AU - Prinz C AD - Lehrstuhl fur Innere Medizin 1, Universitat Witten/Herdecke, Wuppertal, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140825 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antibodies, Neutralizing) RN - 0 (Interleukin-17) RN - 0 (Interleukin-6) RN - 0 (Toll-Like Receptors) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Antibodies, Neutralizing/pharmacology MH - CD4-Positive T-Lymphocytes/immunology MH - Cell Polarity MH - Dendritic Cells/immunology/*microbiology MH - Helicobacter Infections/*immunology MH - Helicobacter pylori/*immunology MH - Humans MH - Interferon-gamma/metabolism MH - Interleukin-10/metabolism MH - Interleukin-12/metabolism MH - Interleukin-17/metabolism MH - Interleukin-6/metabolism MH - Signal Transduction MH - T-Lymphocytes, Regulatory/immunology MH - Toll-Like Receptors/*physiology PMC - PMC4143222 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/08/26 06:00 MHDA- 2015/05/23 06:00 PMCR- 2014/08/25 CRDT- 2014/08/26 06:00 PHST- 2014/05/10 00:00 [received] PHST- 2014/07/14 00:00 [accepted] PHST- 2014/08/26 06:00 [entrez] PHST- 2014/08/26 06:00 [pubmed] PHST- 2015/05/23 06:00 [medline] PHST- 2014/08/25 00:00 [pmc-release] AID - PONE-D-14-20029 [pii] AID - 10.1371/journal.pone.0104804 [doi] PST - epublish SO - PLoS One. 2014 Aug 25;9(8):e104804. doi: 10.1371/journal.pone.0104804. eCollection 2014.