Escherichia coli Shiga toxin 1 enhances il-4 transcripts in bovine ileal intraepithelial lymphocytes

Etienne Moussay, Ivonne Stamm, Anja Taubert, Georg Baljer, Christian Menge*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)


Shiga toxin 1 (Stx1) blocks the activation of bovine peripheral and intraepithelial lymphocytes (IEL), implying that the toxin has the potential to retard the host's immune response during intestinal colonization of cattle with human pathogenic Stx-producing Escherichia coli (STEC). Since Stx1 does not eliminate affected lymphocytes by causing cellular death, we assumed that Stx1 disturbs the integrity of the immune regulatory network. We therefore assessed the impact of Stx1 on the expression of selected chemokine and cytokine genes in vitro by real-time RT-PCR and by quantitation of intracellular cytokine proteins. While Stx1 did not alter the amount of mRNA specific for interleukin (IL)-2, IL-10, gamma interferon (IFN-γ), transforming growth factor beta (TGF-β), IL-8, 10 kDa interferon inducible protein (IP-10), and monocyte chemoattractant protein 1 (MCP-1) in cultured ileal IEL (iIEL), minute concentrations of Stx1 led to an up to 40-fold increase of il-4 transcripts within 6-8 h of incubation. Comparative experiments with peripheral lymphocytes revealed that the effect was specific for iIEL. The enhancement of il-4 transcripts in iIEL was not accompanied by apoptosis but required the enzymatic activity of the holotoxin. Nevertheless, iIEL retained their ability to synthesize proteins in the presence of Stx1: 40% of iIEL could be stimulated to synthesize IFN-γ while less than 10% expressed IL-4 or TGF-β. Furthermore, iIEL were found to produce granulocyte chemoattractants, but the release of these substances was not different in iIEL cultures incubated with or without Stx1. Although Stx1 did not affect the numbers of iIEL producing either cytokine, these findings point to an altered responsiveness of IEL during bovine STEC infections and shed light on the initial effects Stx1 exerts on the local adaptive immune system.

Original languageEnglish
Pages (from-to)367-382
Number of pages16
JournalVeterinary Immunology and Immunopathology
Issue number3-4
Publication statusPublished - 15 Oct 2006
Externally publishedYes


  • Cattle
  • Intraepithelial lymphocytes
  • Shiga toxin 1
  • il-4


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