Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain.

DAVE MN; SILVA JE; ELIÇABE RJ; JERÉZ MB; FILIPPA VP; GORLINO CV,; AUTENRIETH S; AUTENRIETH IB; DI GENARO MS

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2016 vol. 84 p. 3172 - 3181

0019-9567

Yersinia enterocolitica evade 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 YopH-deficient mutant strain (Y. enterocolitica yopH). While the major neutrophil chemoattract CXCL1 mRNA and protein levels were induced by the Y. enterocolitica wild-type (WT) strain in PP, infection with the Y. enterocolitica yopH 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 dyopH infection raised bacterial load in PP. Moreover, the clearance of Y. enterocolitica WT strain was improved when an equal mixture of Y. enterocolitica WT and Y. enterocolitica yopH 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 Y. enterocolitica YopH-deficient strain as an oral vaccine carrier.