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Infection and Immunity, April 2001, p. 2293-2301, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2293-2301.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Salmonella enterica Serovar Typhimurium Induces Cell Death in Bovine Monocyte-Derived Macrophages by Early sipB-Dependent and Delayed sipB-Independent Mechanisms

Renato L. Santos,1 Renée M. Tsolis,1 Andreas J. Bäumler,2 Roger Smith III,1 and L. Garry Adams1,*

Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843-4467,1 and Department of Medical Microbiology and Immunology, College of Medicine, Texas A&M University System Health Science Center, College Station, Texas 77843-11142

Received 14 July 2000/Returned for modification 5 October 2000/Accepted 2 January 2001

It was previously demonstrated that Salmonella enterica serovar Typhimurium induces cell death with features of apoptosis in murine macrophages. Mice infected with Salmonella serovar Typhimurium develop systemic disease without diarrhea, whereas the infection in cattle and in humans is localized and characterized by diarrhea. Considering these clinical disease expression differences between mice and cattle, we investigated whether serovar Typhimurium is cytotoxic for bovine macrophages. Macrophages infected with serovar Typhimurium grown in the logarithmic phase quickly underwent cell death. Macrophages infected with stationary-phase cultures or with a mutant lacking sipB underwent no immediate cell death but did develop delayed cytotoxicity, undergoing cell death between 12 and 18 h postinfection. Both pathways were temporarily blocked by the general caspase inhibitor Z-VAD-Fmk and by the caspase 1 inhibitor Z-YVAD-Fmk. Comparisons of macrophages from cattle naturally resistant or susceptible to intracellular pathogens indicated no differences between these two genetic backgrounds in terms of susceptibility to serovar Typhimurium-induced cell death. We conclude that Salmonella serovar Typhimurium induces cell death in bovine macrophages by two distinct mechanisms, early sipB-mediated and delayed sipB-independent mechanisms.

* 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, April 2001, p. 2293-2301, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2293-2301.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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