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Infection with Shiga toxin-producing Escherichia coli (STEC) may cause hemorrhagic colitis, hemolytic uremic syndrome (HUS) and encephalopathy. The mortality rate derived from HUS adds up to 5% of the cases, and up to 40% when the central nervous system (CNS) is in-volved. In addition to the well-known deleterious effect of Stx, the gram-negative STEC releases lipopolysaccharides (LPS) and may induce a variety of inflammatory responses when released in the gut. Common clinical signs of severe CNS injury include sensorimotor, cognitive, emotional and/or autonomic alterations. In the last few years, a number of drugs have been experimentally employed to establish the pathogenesis of, prevent or treat CNS injury by STEC. The strategies in these approaches focus on: 1) inhibition of Stx production and release by STEC, 2) inhibition of Stx bloodstream transport, 3) inhibition of Stx entry into the CNS parenchyma, 4) blockade of deleterious Stx action in neural cells, and 5) inhibition of immune system activation and CNS inflamma-tion. Fast diagnosis of STEC infection, as well as the establishment of early CNS biomarkers of damage, may be determinants of adequate neuropharmacological treatment in time. Fil: Goldstein Raij, Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Nuñez Goluboay, Krista. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Vasconcelos Esteves Pinto, Alipio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina

Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that produces Shiga toxin (Stx) and causes hemorrhagic colitis. Under some circumstances, Stx produced within the intestinal tract enters the bloodstream, leading to systemic complications that may cause the potentially fatal hemolytic-uremic syndrome. Although retinoids like vitamin A (VA) and retinoic acid (RA) are beneficial to gut integrity and the immune system, the effect of VA supplementation on gastrointestinal infections of different etiologies has been controversial. Thus, the aim of this work was to study the influence of different VA status on the outcome of an EHEC intestinal infection in mice. We report that VA deficiency worsened the intestinal damage during EHEC infection but simultaneously improved survival. Since death is associated mainly with Stx toxicity, Stx was intravenously inoculated to analyze whether retinoid levels affect Stx susceptibility. Interestingly, while VA-deficient (VA-D) mice were resistant to a lethal dose of Stx2, RA-supplemented mice were more susceptible to it. Given that peripheral blood polymorphonuclear cells (PMNs) are known to potentiate Stx2 toxicity, we studied the influence of retinoid levels on the absolute number and function of PMNs. We found that VA-D mice had decreased PMN numbers and a diminished capacity to produce reactive oxygen species, while RA supplementation had the opposite effect. These results are in line with the well-known function of retinoids in maintaining the homeostasis of the gut but support the idea that they have a proinflammatory effect by acting, in part, on the PMN population. Fil: Cabrera, Gabriel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Fernández Brando, Romina Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Abrey Recalde, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Baschkier, Ariela. Direccion Nacional de Instituto de Investigacion. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriologia; Argentina Fil: Vasconcelos Esteves Pinto, Alipio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Neurofisiología; Argentina Fil: Goldstein Raij, Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Neurofisiología; Argentina Fil: Zotta, Elsa. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina Fil: Meiss, Roberto. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Rivas, Marta. Direccion Nacional de Instituto de Investigacion. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriologia; Argentina Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina