IMPACT OF THE VIRULENCE FACTOR YopP ON DEVELOPMENT OF IMMUNE RESPONSE AGAINST YERSINIA ENTEROCOLITICA

SILVA JUAN EDUARDO; DAVICINO ROBERTO; DI GENARO MARÍA SILVIA

Buenos Aires

Congreso; Reunión Conjunta de sociedades de Biosciencias; 2017

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) ; SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) , SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL (SAFE); SOCIEDAD ARGENTINA DE INVESTIGACIÓN BIOQUÍMICA Y BIOLOGÍA MOLECULAR (SAIB); SOCIEDAD ARGENTINA DE FISIOL

Yersinia enterocolitica (Ye) are Gram-negative enteropathogenic bacteria. Ye inject the effector proteins called Yersinia outer proteins (Yops) into host target cells. YopP induces apoptosis in macrophages and dendritic cells (DC). Here, we aimed to compare the invasion properties and immune response induced by YopP-deficient (Ye YopP) and wild type (Ye wt) strains. Therefore, C57BL/6 mice were oragastrically infected with 1-5 x 108 or 5 x 1010 Ye YopP, Ye wt or Ye wt-GFP. After 30, 60, 120 min and 5 days after infection, Peyer?s patches (PP), mesenteric lymph node (MLN) and spleen (S) were obtained. Colony forming units (CFU) were evaluated in the organs at 60 min and 5 days after infection. Cytokines and NF-β were measured by ELISA, and cell infiltration by flow cytometry. Mice infected with Ye YopP showed increased CFU in PP at 60 min (p≤ 0.05), and in MLN and S after 5 days post-infection (p≤ 0.01). Besides, higher amount of pro-inflammatory cytokines (IL-1β, IFN-, TNF, IL-6, and IL-17) (p≤ 0.05), and increased translocation of NF-β (p≤ 0.05) was detected in PP of mice infected with Ye YopP compared to those infected with Ye wt. However, IL-10 decreased after Ye YopP infection (p≤ 0.01). At 5 days after Ye YopP infection, it was found increased frequency and absolute number of macrophage (CD11b+ F4/80+) in PP and MLN (p≤ 0.001), and of neutrophils (CD11b+, Ly6G+) in PP (p≤ 0.01). However, we did not observe differences in the absolute number of macrophages, dendritic cells (CD11c+) and CD11cint CD11b+ inflammatory cells in S at 60 min post-infection. Because we did not found early differences in cell recruitment, we evaluated cells involving on immediate dissemination of Ye. We observed an increased number of CD11c+ CD11b+ CD103+ GFP+ at 60 and 120 min post-infection in S from Ye wt-GFP infected mice (p≤ 0.05). We concluded that YopP could be playing a critical role in Ye infection, controlling the immune response at mucosal entry sites.