title: Yersinia enterocolitica YopP inhibits MAP kinase-mediated antigen uptake in dendritic cells.
abstract: Yersinia enterocolitica (Ye) targets mouse dendritic cells (DCs) and inhibits their ability to trigger T cell activation. Here we have investigated whether Ye might interfere with antigen presentation in DCs. Infection of DCs with the Ye wild-type strain reduced OVA uptake by DCs as demonstrated by flow cytometry and confocal laser scan microscopy. In contrast, DCs infected with Yersinia outer protein P (YopP)-deficient mutant strain rapidly internalized OVA. Furthermore, transfection of DCs with YopP, but not with a cysteine protease deficient YopP-C172A mutant, reduced uptake of OVA. This finding suggests that YopP, a virulence factor of Ye, inhibits OVA uptake by DCs. By the use of MAPK inhibitors we provide evidence that YopP mediates reduction of OVA uptake by its ability to block MAPK signalling pathways in host cells. Using transferrin (Tf) as specific marker for clathrin-mediated endocytosis (CME) and lucifer yellow (LY) as specific marker for macropinocytosis (MP) we could show that YopP inhibits CME, whereas other Yops inhibit MP. In keeping with these data, activation and proliferation of OVA-specific T cells was reduced when DCs were treated with MAPK inhibitors. Together, our data demonstrate that (i) MAPK play an important role in antigen uptake by CME in DCs, and (ii) that YopP inhibits this pathway of antigen uptake in DCs, which might contribute to evasion of adaptive immunity.
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Universität Tübingen, Tübingen, Germany. stella.autenrieth@med.uni-tuebingen.de
authors.forename: Stella E
authors.initials: SE
authors.lastname: Autenrieth
authors.forename: Irena
authors.initials: I
authors.lastname: Soldanova
authors.forename: Roman
authors.initials: R
authors.lastname: Rösemann
authors.forename: Daniela
authors.initials: D
authors.lastname: Gunst
authors.forename: Naima
authors.initials: N
authors.lastname: Zahir
authors.forename: Michael
authors.initials: M
authors.lastname: Kracht
authors.forename: Klaus
authors.initials: K
authors.lastname: Ruckdeschel
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Stefan
authors.initials: S
authors.lastname: Borgmann
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D015008:Yersinia enterocolitica / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; C109227:YopP protein, Yersinia; D020928:Mitogen-Activated Protein Kinases