Modulation of human monocytes by Escherichia coli heat-labile enterotoxin B-subunit; altered cytokine production and its functional consequences.

Abstract

In murine systems, the B subunit of Escherichia coli heat-labile enterotoxin (EtxB) is a potent immunomodulator capable of suppressing Th1-mediated autoimmune diseases. This results from its ability to bind cell surface receptors, principally GM1-ganglioside, and as a consequence down-regulate the pathological T helper type 1 (Th1) response. The capacity of EtxB to alter human T-cell responses has not been investigated. Here we show that EtxB, but not the receptor non-binding mutant EtxB (G33D), triggers the release of interleukin (IL)-10, IL-6 and tumour necrosis factor-alpha (TNF-alpha) by human monocytes. The production of IL-8, transforming growth factor-beta (TGF-beta) or IL-12 was not enhanced by EtxB. Indeed, EtxB was shown to inhibit IL-12 secretion in monocytes stimulated with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) by an IL-10-independent mechanism. When EtxB-treated monocytes were used as antigen presenting cells in an allogeneic mixed lymphocyte reaction (MLR), IL-10 and IFN-gamma production were increased in comparison to levels seen in cultures stimulated with untreated monocytes; proliferation was unaltered. This modulation of the T-cell response was not only evident in the primary MLR triggered by EtxB-treated monocytes, but also upon restimulation of the responding T cells with fresh untreated monocytes; indicating that presentation by EtxB-treated monocytes leads to altered T-cell differentiation. Sorting experiments showed that IL-10 secreting T cells from the MLR cultures were strong suppressors of T-cell proliferation following their addition into a fresh primary MLR.

• Authors: Victor Turcanu, Timothy R Hirst, Neil A Williams
• Journal: Immunology (Immunology) Vol. 106 Issue 3 Pg. 316-25 (Jul 2002) ISSN: 0019-2805 [Print] England
• PMID: 12100719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Bacterial Toxins
• Cytokines
• Enterotoxins
• Escherichia coli Proteins
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Interleukin-12
• heat-labile enterotoxin, E coli

Topics

• Adjuvants, Immunologic
• Bacterial Toxins (immunology)
• Cell Culture Techniques
• Cell Division (immunology)
• Cytokines (biosynthesis)
• Dose-Response Relationship, Immunologic
• Enterotoxins (immunology)
• Escherichia coli (immunology)
• Escherichia coli Proteins
• Humans
• Interleukin-10 (biosynthesis, immunology)
• Interleukin-12 (biosynthesis)
• Interleukin-6 (biosynthesis)
• Lymphocyte Culture Test, Mixed
• Monocytes (immunology)
• Tumor Necrosis Factor-alpha (biosynthesis)