Shiga toxin-producing Escherichia coli (STEC) is a food-borne pathogen that causes hemorrhagic
colitis. Under some circumstances,
Shiga toxin (Stx) produced within the intestinal tract enters the bloodstream, leading to systemic complications that may cause the potentially fatal
hemolytic-uremic syndrome (HUS). Despite STEC human
infection is characterized by acute
inflammation of the colonic mucosa, little is known regarding the role of proinflammatory mediators like
cysteine leukotrienes (cysLTs) in this pathology. Thus, the aim of this work was to analyze whether
leukotriene C4 (
LTC4) influences STEC pathogenesis in mice. We report that exogenous
LTC4 pretreatment severely affected the outcome of STEC gastrointestinal
infection. LTC4-pretreated (
LTC4+) and STEC-infected (STEC+) mice showed an increased intestinal damage by histological studies, and a decreased survival compared to LTC4-non-pretreated (LTC4-) and STEC+ mice.
LTC4+/STEC+ mice that died after the
infection displayed neutrophilia and high
urea levels, indicating that the cause of death was related to Stx2-toxicity. Despite the differences observed in the survival between LTC4+ and LTC4- mice after STEC
infection, both groups showed the same survival after Stx2-intravenous inoculation. In addition,
LTC4 pretreatment increased the permeability of mucosal intestinal barrier, as assessed by
FITC-dextran absorption experiments. Altogether these results suggest that
LTC4 detrimental effect on STEC
infection is related to the increased passage of pathogenic factors to the bloodstream. Finally, we showed that STEC
infection per se increases the endogenous
LTC4 levels in the gut, suggesting that this inflammatory mediator plays a role in the pathogenicity of STEC
infection in mice, mainly by disrupting the mucosal epithelial barrier.