Salmonella typhimurium induces apoptosis in human monocyte-derived macrophages

Xin Zhou, Nicholas Mantis, Xiao Ru Zhang, Douglas A. Potoka, Simon C. Watkins, Henri R. Ford

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Salmonella species represent a leading cause of gastroenteritis worldwide. More recently, they have been proposed as putative vaccine delivery vehicles in humans. Oral infection with Salmonella leads to invasion of the intestinal epithelial barrier and subsequent interaction with mucosal macrophages. In this study, we investigated the fate of Salmonella typhimurium-infected human macrophages differentiated from blood monocytes by GM-CSF. Wild type S. typhimurium strain SL1344 induced macrophage surface blebbing and caused the release of host cytoplasmic lactate dehydrogenase beginning 30 min post-infection. Three hours later more than 80% of the macrophages in the culture were killed. In contrast, during the same period, macrophages infected with the non-invasive S. typhimurium strain BJ66 remained viable. Chromatin fragmentation is a hallmark of cells undergoing apoptosis. Using TUNEL analysis, we observed chromatin fragmentation in macrophages infected with SL1344 but not in BJ66 infected cells. Consistent with this observation, we found that pretreatment of human macrophages with an inhibitor of caspase-3, a member of the pro-apoptotic enzyme family shown to be involved in S. typhimurium-induced killing of mouse macrophages, reduced SL1344-mediated cytotoxicity by 40%. Our study provides the first evidence that invasive S. typhimurium induces apoptosis in human macrophages that were differentiated from blood monocytes by GM-CSF, and that cell death is a caspase-dependent phenomenon.

Original languageEnglish (US)
Pages (from-to)987-995
Number of pages9
JournalMicrobiology and Immunology
Volume44
Issue number12
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Apoptosis
  • Human macrophage
  • Salmonella typhimurium

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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