Leukotriene C4 increases the susceptibility of adult mice to Enterohemorragic Escherichia Coli infection

GABRIEL CABRERA; ROMINA J. FERNÁNDEZ-BRANDO; MARÍA PILAR MEJÍAS; MARÍA VICTORIA RAMOS; MARÍA JIMENA ABREY-RECALDE; SILVIA VANZULLI; MÓNICA VERMEULEN; MARINA S. PALERMO

Mar del Plata

Congreso; LIX Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica y LXII Reunión Científica Anual de la Sociedad Argentina de Inmunología,; 2014

Sociedad Argentina de Inmunología,

Shiga-toxin (Stx) producing Escherichia coli (EHEC) strains can cause a broad spectrum of human diseases, including the life-threatening hemolytic uremic syndrome (HUS). Despite EHEC infection is characterized by acute inflammation of the colonic mucosa, little is known regarding the role of proinflammatory mediators like cysteine leukotrienes (LTC4) in this pathology. Thus, the aim of this work was to analyze whether LTC4 influence EHEC pathogenesis in mice. First, BALB/c mice were pretreated with exogenous LTC4 (0,01uM) before EHEC intragastric infection (5-7x1011 CFU of EHEC/Kg of body weight). LTC4-treated (LTC4+) EHEC-infected (EHEC+) mice showed the highest intestinal damage, as assessed by histology, displaying submucosal infiltration and a high number of apoptotic epithelial cells. In accordance, LTC4+/EHEC+ mice showed a decreased survival rate as compared to LTC4-non-treated (LTC4-) EHEC+ mice. Survival: LTC4+/EHEC+= 62,5%, n=16; LTC4-/EHEC+=93,7% n=16, p<0,05. Both LTC4+ and LTC4- non-infected mice (EHEC-) showed 100% survival. In addition, LTC4+/EHEC+ mice that died after the infection (died) showed clinical parameters related to Stx2 toxicity, including neutrophilia and high urea levels: (% neutrophils in blood±DS; n): LTC4+/EHEC+ (died) 40,0±18,1, n=6; LTC4+/EHEC+ (survivors) 33,0±16,2, n=10; LTC4-/EHEC+ (survived) 22,5±8,2, n=15; LTC4+/EHEC-: 13,0±5,1, n=6; LTC4-/EHEC- 15,7±6,1, n=6, (p<0, LTC4+/EHEC- (died) vs LTC4+/EHEC+ (survivors).Finally, ELISA studies showed that EHEC-ingestion increased per se the endogenous gut levels of LTC4 at 96 h post infection. (pg/ml LTC4±DS, n) EHEC+ 1205±185, n=4; EHEC- 923±217, n=4, (one experiment out of two is shown, p<0,05, ANOVA in groups), while LTB4 did not show differences.Taking together, our results suggest that LTC4 plays a role increasing the pathogenicity of EHEC intragastric infection in mice, mainly by affecting intestinal mucosal integrity