title: Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain.
abstract: Yersinia enterocolitica evades the immune response by injecting Yersinia outer proteins (Yops) into the cytosol of host cells. YopH is a tyrosine phosphatase critical for Yersinia virulence. However, the mucosal immune mechanisms subverted by YopH during in vivo orogastric infection with Y. enterocolitica remain elusive. The results of this study revealed neutrophil recruitment to Peyer's patches (PP) after infection with a YopH-deficient mutant strain (Y. enterocolitica ΔyopH). While the Y. enterocolitica wild-type (WT) strain in PP induced the major neutrophil chemoattractant CXCL1 mRNA and protein levels, infection with the Y. enterocolitica ΔyopH mutant strain exhibited a higher expression of the CXCL1 receptor, CXCR2, in blood neutrophils, leading to efficient neutrophil recruitment to the PP. In contrast, migration of neutrophils into PP was impaired upon infection with Y. enterocolitica WT strain. In vitro infection of blood neutrophils revealed the involvement of YopH in CXCR2 expression. Depletion of neutrophils during Y. enterocolitica ΔyopH infection raised the bacterial load in PP. Moreover, the clearance of WT Y. enterocolitica was improved when an equal mixture of Y. enterocolitica WT and Y. enterocolitica ΔyopH strains was used in infecting the mice. This study indicates that Y. enterocolitica prevents early neutrophil recruitment in the intestine and that the effector protein YopH plays an important role in the immune evasion mechanism. The findings highlight the potential use of the Y. enterocolitica YopH-deficient strain as an oral vaccine carrier.
authors.affiliation: Multidisciplinary Institute of Biological Investigations-San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations-National University of San Luis (CONICET-UNSL), San Luis, Argentina.|Faculty of Chemistry, Biochemistry and Pharmacy, UNSL, San Luis, Argentina.
authors.forename: Mabel N
authors.initials: MN
authors.lastname: Dave
authors.affiliation: Multidisciplinary Institute of Biological Investigations-San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations-National University of San Luis (CONICET-UNSL), San Luis, Argentina.|Faculty of Chemistry, Biochemistry and Pharmacy, UNSL, San Luis, Argentina.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Silva
authors.affiliation: Multidisciplinary Institute of Biological Investigations-San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations-National University of San Luis (CONICET-UNSL), San Luis, Argentina.|Faculty of Chemistry, Biochemistry and Pharmacy, UNSL, San Luis, Argentina.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Eliçabe
authors.affiliation: Multidisciplinary Institute of Biological Investigations-San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations-National University of San Luis (CONICET-UNSL), San Luis, Argentina.|Faculty of Chemistry, Biochemistry and Pharmacy, UNSL, San Luis, Argentina.
authors.forename: María B
authors.initials: MB
authors.lastname: Jeréz
authors.affiliation: Multidisciplinary Institute of Biological Investigations-San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations-National University of San Luis (CONICET-UNSL), San Luis, Argentina.|Faculty of Chemistry, Biochemistry and Pharmacy, UNSL, San Luis, Argentina.
authors.forename: Verónica P
authors.initials: VP
authors.lastname: Filippa
authors.affiliation: Multidisciplinary Institute of Biological Investigations-San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations-National University of San Luis (CONICET-UNSL), San Luis, Argentina.|Faculty of Chemistry, Biochemistry and Pharmacy, UNSL, San Luis, Argentina.
authors.forename: Carolina V
authors.initials: CV
authors.lastname: Gorlino
authors.affiliation: Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Stella
authors.identifier: http://orcid.org/0000-0003-4054-9041
authors.initials: S
authors.lastname: Autenrieth
authors.affiliation: Institute of Medical Microbiology and Hygiene, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
authors.affiliation: Multidisciplinary Institute of Biological Investigations-San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations-National University of San Luis (CONICET-UNSL), San Luis, Argentina sdigena@unsl.edu.ar.|Faculty of Chemistry, Biochemistry and Pharmacy, UNSL, San Luis, Argentina.
authors.forename: María S
authors.initials: MS
authors.lastname: Di Genaro
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D010581:Peyer's Patches / Q000166:cytology*; D019707:Receptors, Chemokine / Q000378:metabolism; D014774:Virulence / Q000502:physiology; D015009:Yersinia Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015008:Yersinia enterocolitica / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D019743:Chemokines, CXC; D019707:Receptors, Chemokine