Journal Article

MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis

KANAI TAKANORI, TOTSUKA TERUJI, ISHIKURA TAKAHIRO, AKIRA SHIZUO, WATANABE MAMORU, TAKEDA KIYOSHI, URAUSHIHARA KOJI, ARAKI AKIHIRO, IIYAMA RYOICHI, MAKIT SHIN

2005

Overview

Gut commensal microbes affect the development and activation of the mucosal and systemic immune systems. However, the exact molecular mechanism of these microbes that is involved in the development of colitis remains unclear. The present study was conducted to determine the distinct role of the innate immune system in the development of a dextran sulfate sodium (DSS) colitis model in MyD88(-/-) mice, because myeloid differentiation protein (MyD88) is a major adaptor molecule essential for signaling via Toll-like receptors (TLRs). To this end, MyD88(-/-) and wild-type (WT) mice received sterile distilled water containing 1.2% DSS for 8 days. The survival rate, total clinical score (body weight loss, stool consistency, and rectal bleeding), colon length, and histological score were assessed. The expression of surface markers (F4/80 and CD4) on infiltrating lamina propria mononuclear cells was analyzed immunohistochemistrically. MyD88(-/-) mice exhibited increased susceptibility to DSS-induced colitis, as reflected by significantly higher lethality and higher clinical and histological scores, and more severe colonic shortening compared to WT mice. Immunohistochemical analysis revealed a significant increase of both F4/80+ macrophages and CD4+ T cells in the inflamed mucosa in DSS-fed MyD88(-/-) mice compared to DSS-fed WT mice. These findings suggest that, via MyD88 signaling, the innate immune system in the gut plays an important protective role in colitis.

• Publisher: Springer Nature B.V
• Subject: Adaptor Proteins, Signal Transducing - deficiency / Adaptor Proteins, Signal Transducing - drug effects / Animals / Antigens, CD - drug effects / Antigens, CD - metabolism / Antigens, Differentiation - drug effects / Antigens, Differentiation, T-Lymphocyte - drug effects / Antigens, Differentiation, T-Lymphocyte - metabolism / Antiviral Agents - administration & dosage / Antiviral Agents - adverse effects / CD4-Positive T-Lymphocytes - drug effects / CD4-Positive T-Lymphocytes - metabolism / Colitis - chemically induced / Colitis - metabolism / Colitis - mortality / Dextran Sulfate - administration & dosage / Dextran Sulfate - adverse effects / Disease Models, Animal / Disease Susceptibility / Dose-Response Relationship, Drug / DSS-induced colitis / Immunohistochemistry / inflammation / Inflammatory Bowel Diseases - chemically induced / Inflammatory Bowel Diseases - metabolism / Inflammatory Bowel Diseases - mortality / innate immune system / Interleukin-18 Receptor alpha Subunit / Intestinal Mucosa - drug effects / Intestinal Mucosa - metabolism / Intestinal Mucosa - pathology / Lectins, C-Type / luminal bacterial flora / Macrophages - drug effects / Macrophages - metabolism / Male / Mice / MyD88 / Myeloid Differentiation Factor 88 / Receptors, Immunologic - deficiency / Receptors, Immunologic - drug effects / Receptors, Interleukin - drug effects / Receptors, Interleukin - metabolism / Receptors, Interleukin-18 / Receptors, Interleukin-2 - drug effects / Receptors, Interleukin-2 - metabolism / Severity of Illness Index