Intestinal Macrophages and Microflora in Inflammatory Bowel Diseases

Abstract

Macrophages (MΦs), the major population of tissue-resident mononuclear phagocytes, play key roles in bacterial recognition and elimination as well as in polarization of innate and adaptive immunities. Since the intestinal mucosa of the gut is always exposed to numerous enteric bacteria including both pathogenic and non-pathogenic bacteria, it is considered that the gut may possess regulatory mechanisms preventing excessive inflammatory responses. On the other hand, it has become evident that abnormal innate immune responses to enteric bacteria are responsible for the pathogenesis of IBD. It became evident by our present study that intestinal MΦs from wild-type mice produced large amounts of IL-10 but failed to produce IL-12 and IL-23 in response to enteric bacteria. In contrast, in IL-10^-/-mice, intestinal MΦs differentiated into abnormal phenotypes under an IL-10 deficient environment, and produced abnormally large amounts of IL-12 and IL-23 in response to enteric bacteria. These results suggest that intestinal MΦs act as anti-inflammatory MΦs, and suppress excess inflammation induced by enteric bacteria in the normal state. In IL-10^-/-mice, however, intestinal MΦs differentiated into abnormal phenotypes, and enteric bacteria recognition by these abnormally differentiated subsets of intestinal MΦ may lead to Th1-dominant colitis via IL-12 and IL-23 hyperproduction.