Sera from patients with Crohn’s disease break bacterial lipopolysaccharide tolerance of human intestinal epithelial cells via MD-2 activity

• Published in: Innate immunity (London, England) Vol. 16; no. 6; pp. 381 - 390
• Main Authors: Seksik, Philippe, Sokol, Harry, Grondin, Virginie, Adrie, Christophe, Duboc, Henri, Pigneur, Benedicte, Thomas, Ginette, Beaugerie, Laurent, Trugnan, Germain, Masliah, Joelle, Bachelet, Maria
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.12.2010
• Subjects: Adult; Bacteria; Chemical Sciences; Colitis, Ulcerative - blood; Colitis, Ulcerative - immunology; Crohn Disease - blood; Crohn Disease - immunology; Female; HT29 Cells; Humans; Immune Tolerance - drug effects; Immune Tolerance - immunology; Immunity, Mucosal - drug effects; Immunity, Mucosal - immunology; Intestinal Mucosa - drug effects; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Lipopolysaccharides - pharmacology; Lymphocyte Antigen 96 - blood; Lymphocyte Antigen 96 - immunology; Male; Middle Aged; Organic chemistry; MD-2; intestinal epithelial cells; lipopolysaccharide tolerance; inflammatory bowel disease
• ISSN: 1753-4259; 1753-4267; 1743-2839
• DOI: 10.1177/1753425909357076

Myeloid differentiation (MD)-2 is linked to the cell surface as a Toll-like receptor (TLR) 4-bound protein though may also function as a soluble receptor to enable the lipopolysaccharide (LPS)-driven response. We recently demonstrated the importance of MD-2 either as a cell-associated or as a soluble receptor in the control of intestinal epithelial cell response toward LPS. High levels of circulating MD-2 were recently proposed as a risk factor for infectious/ inflammatory diseases as septic shock. We hypothesized that MD-2 might be present in sera from patients with inflammatory bowel disease and have pathogenic consequences. We analysed MD-2 activity in sera from patients with inflammatory bowel disease or from healthy subjects. We measured MD-2 activity as the capacity to mediate LPS-driven stimulation of intestinal epithelial cells (HT29). We found that sera from patients with inflammatory bowel disease, particularly Crohn’s disease, endowed HT29 cells with a markedly higher LPS-dependent stimulating capacity as compared to sera from healthy subjects. The effect of sera was specific for LPS activation and was reduced in the presence of anti-MD-2, and anti-TLR4 antibodies. We conclude that sera from patients with inflammatory bowel disease might contain increased MD-2. This might result in higher local availability of the protein leading to a loss of tolerance toward gut microbiota.