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Infection and Immunity, July 2001, p. 4610-4617, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4610-4617.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Salmonella-Induced Cell Death Is Not Required for Enteritis in Calves

Renato L. Santos,1 Renée M. Tsolis,1 Shuping Zhang,1 Thomas A. Ficht,1 Andreas J. Bäumler,2 and L. Garry Adams1,*

Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University,1 and Department of Medical Microbiology and Immunology, College of Medicine, Texas A&M University Health Science Center,2 College Station, Texas 77843

Received 4 December 2000/Returned for modification 29 January 2001/Accepted 13 March 2001

Salmonella enterica serovar Typhimurium causes cell death in bovine monocyte-derived and murine macrophages in vitro by a sipB-dependent mechanism. During this process, SipB binds and activates caspase-1, which in turn activates the proinflammatory cytokine interleukin-1beta through cleavage. We used bovine ileal ligated loops to address the role of serovar Typhimurium-induced cell death in induction of fluid accumulation and inflammation in this diarrhea 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 other two groups (four calves each) were inoculated with 0.75 × 109 CFU of either wild-type serovar Typhimurium (strain IR715) or a sopB mutant per loop in 12 loops. Hematoxylin and eosin-stained sections were scored for inflammation, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells were detected in situ. Fluid accumulation began at 3 h postinfection (PI). Inflammation was detected in all infected loops at 1 h PI. The area of TUNEL-labeled cells in the wild-type infected 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 wild type, but it was attenuated for induction of fluid secretion and inflammation. Our results indicate that serovar Typhimurium-induced cell death is not required to trigger an early inflammatory response and fluid accumulation in the ileum.

* Corresponding author. Mailing address: Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4467. Phone: (979) 845-5092. Fax: (979) 845-5088. E-mail: gadams{at}cvm.tamu.edu.

Infection and Immunity, July 2001, p. 4610-4617, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4610-4617.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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