Salmonella-induced cell death is not required for enteritis in calves

Salmonella enterica serovar Typhimurium causes cell death in bovine monocyt e-derived and murine macrophages in vitro by a sipB-dependent mechanism. Du ring this process, SipB binds and activates caspase-1, which in turn activa tes the proinflammatory cytokine interleukin-lp through cleavage. We used b ovine ileal ligated loops to address the role of serovar Typhimurium-induce d cell death in induction of fluid accumulation and inflammation in this di arrhea model. Twelve perinatal calves had 6- to 9-cm loops prepared in the terminal ileum, They were divided into three groups: one group received an intralumen injection of Luria-Bertani broth as a control in 12 loops. The o ther two groups (four calves each) were inoculated with 0.75 x 10(9) CFU of either wild-type serovar Typhimurium (strain IR715) or a sopB mutant per l oop in 12 loops. Hematoxylin and eosin-stained sections were scored for inf lammation, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin ni ck end labeling (TUNEL)-positive cells were detected in situ, Fluid accumul ation began at 3 h postinfection (PI), Inflammation was detected in all inf ected loops at 1 h PI. The area of TUNEL-labeled cells in the wild-type inf ected loops was significantly higher than that of the controls at 12 h PI, when a severe inflammatory response and tissue damage had already developed . The sopB mutant induced the same amount of TUNEL-positive cells as the wi ld type, but it was attenuated for induction of fluid secretion and inflamm ation. Our results indicate that serovar Typhimurium-induced cell death is not required to trigger an early inflammatory response and fluid accumulati on in the ileum.