Involvement of Innate Immunity in the Development of Inflammatory and Autoimmune Diseases

Abstract

Initial events and effector mechanisms of most inflammatory and autoimmune diseases remain largely unknown. Dysfunction of the innate and adaptive immune systems associated with mucosae (the major interface between the organism and its environment, e.g., microbiota, food) can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Animal models help in elucidating the etiology and pathogenetic mechanisms of human diseases, such as the inflammatory bowel diseases, Crohn's disease and ulcerative colitis, severe chronic diseases affecting the gut. To study the role of innate immunity and gut microbiota in intestinal inflammation, colitis was induced by dextran sulfate sodium (DSS) in mice with severe combined immunodeficiency (SCID). Conventionally reared (microflora-colonized) SCID mice displayed severe inflammation like that seen in immunocompetent Balb/c mice, whereas only minor changes appeared in the intestinal mucosa of DSS-fed gnotobiotic germ-free SCID mice. The presence of microflora facilitates the inflammation in DSS-induced colitis that develops in immunodeficient SCID mice, that is, in the absence of T and B lymphocytes. Celiac disease, a chronic autoimmune small bowel disorder, afflicts genetically susceptible individuals with wheat gluten intolerance. We showed that, in contrast with any other food proteins, wheat gliadin and its peptic fragments activate mouse macrophages and human monocytes to produce proinflammatory cytokines through the nuclear factor-kappaB signaling pathway. Activation of innate immunity cells by food proteins or components from gut microbiota thus could participate in the impairment of intestinal mucosa and the development of intestinal and/or systemic inflammation.

Dendritic cells expressing immunoreceptor CD300f are critical for controlling chronic gut inflammation

“…It is generally thought that DSS induces epithelial cell death, thereby disrupting the intestinal epithelial barrier, leading to infiltration of gut microorganisms into the mucosa (19). This activates tissue-resident macrophages and DCs to recruit neutrophils, which transiently elevate inflammatory responses in order to defend the host against microbial assault (30,31). After performing their antimicrobial functions, neutrophils undergo apoptosis, and are subsequently removed by phagocytes, mainly macrophages (32,33), promoting resolution of acute inflammation and a return to homeostasis (25).…”

The Role of Dendritic Cells in the Development of Acute Dextran Sulfate Sodium Colitis

“…Because this model appears to be independent of a T cell response, as colitis can be induced in mice with severe combined immunodeficiency lacking T and B cells (11), it is an appropriate tool to study the innate mechanisms of colitis (13). The mechanism of inflammation is believed to involve the direct toxic effect of DSS on colonic epithelium leading to the direct activation of intestinal macrophages by DSS (14). However, the role of DCs in the induction of DSS colitis has not been directly demonstrated.…”

Expression of Toll-like Receptor 2 (TLR2), TLR4, and CD14 in Biopsy Samples of Patients With Inflammatory Bowel Diseases: Upregulated Expression of TLR2 in Terminal Ileum of Patients With Ulcerative Colitis

“…Despite the long-standing interest of investigators, etiology and pathogenesis of IBD remain unclear. IBDs seem to involve interactions among immune, environmental, and genetic factors, with the combination of these factors resulting in induction of inflammation, subsequent mucosal lesions, and their repair (Tlaskalova-Hogenova et al 2005).…”