title: Role of β1 integrins and bacterial adhesins for Yop injection into leukocytes in Yersinia enterocolitica systemic mouse infection.
abstract: Injection of Yersinia outer proteins (Yops) into host cells by a type III secretion system is an important immune evasion mechanism of Yersinia enterocolitica (Ye). In this process Ye invasin (Inv) binds directly while Yersinia adhesin A (YadA) binds indirectly via extracellular matrix (ECM) proteins to β1 integrins on host cells. Although leukocytes turned out to be an important target of Yop injection by Ye, it was unclear which Ye adhesins and which leukocyte receptors are required for Yop injection. To explain this, we investigated the role of YadA, Inv and β1 integrins for Yop injection into leukocytes and their impact on the course of systemic Ye infection in mice. Ex vivo infection experiments revealed that adhesion of Ye via Inv or YadA is sufficient to promote Yop injection into leukocytes as revealed by a β-lactamase reporter assay. Serum factors inhibit YadA- but not Inv-mediated Yop injection into B and T cells, shifting YadA-mediated Yop injection in the direction of neutrophils and other myeloid cells. Systemic Ye mouse infection experiments demonstrated that YadA is essential for Ye virulence and Yop injection into leukocytes, while Inv is dispensable for virulence and plays only a transient and minor role for Yop injection in the early phase of infection. Ye infection of mice with β1 integrin-depleted leukocytes demonstrated that β1 integrins are dispensable for YadA-mediated Yop injection into leukocytes, but contribute to Inv-mediated Yop injection. Despite reduced Yop injection into leukocytes, β1 integrin-deficient mice exhibited an increased susceptibility for Ye infection, suggesting an important role of β1 integrins in immune defense against Ye. This study demonstrates that Yop injection into leukocytes by Ye is largely mediated by YadA exploiting, as yet unknown, leukocyte receptors.
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Deuschle
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Keller
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Siegfried
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Manncke
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Spaeth
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Köberle
authors.affiliation: Interfakultäres Institut für Zellbiologie und Immunologie, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Doreen
authors.initials: D
authors.lastname: Drechsler-Hake
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Reber
authors.affiliation: Max Planck Institut für Biochemie, Martinsried, Germany.
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Böttcher
authors.affiliation: Interfakultäres Institut für Zellbiologie und Immunologie, Eberhard Karls Universität, Tübingen, Germany; Medizinische Klinik, Innere Medizin II, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Stella E
authors.initials: SE
authors.lastname: Autenrieth
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany. Electronic address: erwin.bohn@med.uni-tuebingen.de.
authors.forename: Erwin
authors.initials: E
authors.lastname: Bohn
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Schütz
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000502:physiology*; D000483:Alleles; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage*; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D007962:Leukocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D015009:Yersinia Infections / Q000097:blood*; D015008:Yersinia enterocolitica
chemical_list: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D019012:Integrin beta1
keywords: Integrins; Invasin; Mouse infection; Type III secretion system; YadA; Yersinia