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

Yersinia enterocolitica evades the immune response by injectingYersinia outer proteins (Yops) into the cytosol of host cells. YopH is a tyrosine phosphatase critical forYersinia virulence. However, the mucosal immune mechanisms subverted by YopH duringin vivo orogastric infection withY. 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 theY. enterocolitica wild-type (WT) strain in PP induced the major neutrophil chemoattractant CXCL1 mRNA and protein levels, infection with theY. 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 withY. enterocolitica WT strain.In vitro infection of blood neutrophils revealed the involvement of YopH in CXCR2 expression. Depletion of neutrophils duringY. enterocolitica ΔyopH infection raised the bacterial load in PP. Moreover, the clearance of WTY. enterocolitica was improved when an equal mixture ofY. enterocolitica WT andY. enterocolitica ΔyopH strains was used in infecting the mice. This study indicates thatY. 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 theY. enterocolitica YopH-deficient strain as an oral vaccine carrier.