HUS associated to infections with EHEC/STEC. Analysis of the immune response

ALAN M BERNAL; JOHANNA MONTAÑEZ; ANDREA C BRUBALLA; GABRIELA A FIORENTINO; GONZALO E PINEDA ; VERÓNICA FERNÁNDEZ; LAURA DELAPLACE; M VICTORIA RAMOS; ROMINA J FERNÁNDEZ-BRANDO; MARINA S PALERMO

Los Cocos

Otro; Advanced Course on Mucosal Immunology (ACMI 2018); 2018

LAMIG - SMI - UNC - UNLP

We are studying the local inflammatory response into the intestinal microenvironment during EHEC/STEC infections. The GALT not only protects the organism from the invasion and systemic spread of pathogens and limits the level of penetration of commensal microorganisms, but must also differentiate the former from the latter in order to don´t generate unnecessary or harmful immune responses. This differential capacity is linked to the ability of pathogens to replicate and colonize the mucosal surface, and the inflammatory local responses that pathogens induce. However, this inflammatory response may contribute to epithelial damage and, in the context of STEC infections, the induction of shiga toxin production. The understanding of the pathogenesis during first phases of infection with EHEC , will allow to go ahead in the development of specific treatments that should be implemented when the infection is limited to the intestine. To this end, we propose to study the role of different innate T cell populations cells (InT) in the pathogenesis of HUS and the inflammatory immune response.For this end we used the mouse model at weaning, when they are susceptible to EHEC strains and develop systemic manifestations of HUS and death in a percentage of the mice (Brando, Miliwebsky et al., 2008). Previously we demonstrate increase in the expression of CD69 in both LB and LT in the Peyer Plates (PP) at 12 h post-bacterial inoculation and a significant decrease in the expression of CD62L in mesenteric lymph nodes (MLN) at 24 h post-bacterial inoculation of the inoculated animals with EHEC compared with the control. Both parameters are indicators of lymphocyte activation as a consequence of bacterial inoculation. As preliminary results we have observed a significant difference in strain susceptibility between BALB/c and C57Bl mice. This difference was associated to IL-1 production level and Th17 induction in PP from the small intestine. We are interested in studying IL-17-IL-22 axis during EHEC infection using this model of infection in different KO and KI mice.