YopP modulates bacterial virulence and systemic dissemination in Peyer´s patches during murine Yersinia...

Yersinia enterocolitica (Ye) typically causes gastroenteritis and mesenteric lymphadenitis and can also spread extra-intestinally. Yersinia outer protein P (YopP) has been shown to induce cytotoxicity and suppress pro-inflammatory responses in in vitro studies. However, the role of YopP during in vivo Ye infection remains incompletely understood. Here, we show that, contrary to expectations for a virulence factor, a YopP-deficient strain (Ye ΔyopP) increases bacterial dissemination from Peyer's patches (PP) to mesenteric lymph nodes (MLN) and the spleen in intragastrically infected mice. Additionally, inhibition of cytotoxicity by suramin treatment in mice promoted wild-type Ye (Ye WT) dissemination to levels comparable to Ye ΔyopP. Moreover, the absence of YopP enhanced neutrophil and macrophage infiltration and increased pro-inflammatory cytokine production in PP, while decreasing IL-10 levels in PP, MLN and the spleen. Notably, the CD11b⁺ dendritic cell (DC) subpopulation in PP following Ye ∆yopP infection did not reach the levels observed in Ye WT. However, Ye-carrying DCs were significantly elevated after infection with GFP-expressing Ye ∆yopP (Ye ∆yopP GFP⁺). Blocking DC migration by FTY720 treatment in Ye ΔyopP-infected mice significantly reduced the MLN bacterial burden, indicating that YopP regulates Ye-transporting DCs from PP to MLN. Overall, our findings provide insights into how YopP participates in host-pathogen interactions, seemingly benefiting the host while simultaneously facilitating bacterial evasion from early immune clearance. These findings contribute to understanding the impact of YopP on the clinical outcome of Ye infection.