TY - JOUR
T1 - Escherichia coli Shiga toxin 1 enhances il-4 transcripts in bovine ileal intraepithelial lymphocytes
AU - Moussay, Etienne
AU - Stamm, Ivonne
AU - Taubert, Anja
AU - Baljer, Georg
AU - Menge, Christian
N1 - Funding Information:
We thank Paul Sopp, Institute for Animal Health, Compton, Newbury, UK for helpful discussions. Heike Schoepe, Institute for Hygiene and Infectious Diseases of Animals, is acknowledged for her assistance in statistical analysis. This work was supported by grants from the Deutsche Forschungsgemeinschaft to E.M. and C.M. (Sonderforschungsbereich 535).
PY - 2006/10/15
Y1 - 2006/10/15
N2 - 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.
AB - 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.
KW - Cattle
KW - Intraepithelial lymphocytes
KW - Shiga toxin 1
KW - il-4
UR - http://www.scopus.com/inward/record.url?scp=33747841268&partnerID=8YFLogxK
U2 - 10.1016/j.vetimm.2006.06.007
DO - 10.1016/j.vetimm.2006.06.007
M3 - Article
C2 - 16879873
AN - SCOPUS:33747841268
SN - 0165-2427
VL - 113
SP - 367
EP - 382
JO - Veterinary Immunology and Immunopathology
JF - Veterinary Immunology and Immunopathology
IS - 3-4
ER -