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While in most cases the infection remains asymptomatic, 10% of infected individuals develop gastric pathologies and 1\u20133% progress to gastric cancer. Although\n                      <jats:italic>H. pylori<\/jats:italic>\n                      induces severe inflammatory responses, the host\u2019s immune system fails to clear the pathogen and\n                      <jats:italic>H. pylori<\/jats:italic>\n                      can persist in the human stomach for decades. As suppressor of cytokine signaling (SOCS) proteins are important feedback regulators limiting inflammatory responses, we hypothesized that\n                      <jats:italic>H. pylori<\/jats:italic>\n                      could modulate the host\u2019s immune responses by inducing SOCS expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The phenotype of human monocyte-derived DCs (moDCs) infected with\n                      <jats:italic>H. pylori<\/jats:italic>\n                      was analyzed by flow cytometry and multiplex technology. SOCS expression levels were monitored by qPCR and signaling studies were conducted by means of Western blot. For functional studies, RNA interference-based silencing of\n                      <jats:italic>SOCS1\u20133<\/jats:italic>\n                      and co-cultures with CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We show that\n                      <jats:italic>H. pylori<\/jats:italic>\n                      positive gastritis patients express significantly higher\n                      <jats:italic>SOCS3<\/jats:italic>\n                      , but not\n                      <jats:italic>SOCS1<\/jats:italic>\n                      and\n                      <jats:italic>SOCS2<\/jats:italic>\n                      , levels compared to\n                      <jats:italic>H. pylori<\/jats:italic>\n                      negative patients. Moreover, infection of human moDCs with\n                      <jats:italic>H. pylori<\/jats:italic>\n                      rapidly induces\n                      <jats:italic>SOCS3<\/jats:italic>\n                      expression, which requires the type IV secretion system (T4SS), release of TNF\u03b1, and signaling via the MAP kinase p38, but appears to be independent of TLR2, TLR4, MEK1\/2 and STAT proteins. Silencing of\n                      <jats:italic>SOCS3<\/jats:italic>\n                      expression in moDCs prior to\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection resulted in increased release of both pro- and anti-inflammatory cytokines, upregulation of PD-L1, and decreased T-cell proliferation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study shows that\n                      <jats:italic>H. pylori<\/jats:italic>\n                      induces SOCS3 via an autocrine loop involving the T4SS and TNF\u03b1 and p38 signaling. Moreover, we demonstrate that high levels of SOCS3 in DCs dampen PD-L1 expression on DCs, which in turn drives T-cell proliferation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-020-00655-1","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T15:02:54Z","timestamp":1601996574000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["H. pylori modulates DC functions via T4SS\/TNF\u03b1\/p38-dependent SOCS3 expression"],"prefix":"10.1186","volume":"18","author":[{"given":"Muamera","family":"Sarajlic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Neuper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Vetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Schaller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Klicznik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris K.","family":"Gratz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silja","family":"Wessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Posselt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0984-204X","authenticated-orcid":false,"given":"Jutta","family":"Horejs-Hoeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"key":"655_CR1","doi-asserted-by":"crossref","first-page":"5024","DOI":"10.1073\/pnas.0308386101","volume":"101","author":"S Schreiber","year":"2004","unstructured":"Schreiber S, Konradt M, Groll C, Scheid P, Hanauer G, Werling H-O, Josenhans C, Suerbaum S. 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