Chapter 19 : Neuroimmune Interactions and Pathogenesis of Intestinal Inflammation in Infectious Diseases

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The attachment of bacteria to mucosal surfaces is the initial event in the pathogenesis of several bacterial infections in the gastrointestinal tract. Macrophages also express substance P (SP) mRNA, which can be upregulated, leading to the release of SP when exposed to bacterial lipopolysaccharide (LPS) in vitro or during intestinal inflammation in vivo. Neuroimmune interactions and the enteric nervous system also play a major role in the pathogenesis of intestinal secretion due to infection. toxin-mediated diarrhea and enterocolitis represent one of the best disease models, demonstrating how neuroimmune interactions modulate intestinal enterotoxin responses. Interestingly, mast cell-deficient mice have reduced toxin-A-associated ileal secretion and mucosal neutrophil infiltration, providing direct evidence of the importance of these multifunctional cells in the pathogenesis of enterotoxin-induced inflammatory diarrhea. Based on these considerations, macrophage-dependent mechanisms participate in the pathogenesis of toxin A-mediated enterocolitis. Studies using the and animal models of parasitic infections provided important information not only on the pathophysiology of these diseases, but also on the outcome of immune cell-nerve interactions in the pathogenesis of diarrhea and intestinal inflammation. Valuable information from use of these models has had wide application in studies involving neuroimmune interactions in other forms of infectious diarrhea and inflammation. The successful inhibition of several types of infectious diarrhea and inflammation by neuropeptide and neuropeptide receptor antagonists in animal models opens the possibility that these or similar antagonists may be beneficial in the amelioration of the intestinal inflammation in human infection.

Citation: Pothoulakis C. 2003. Neuroimmune Interactions and Pathogenesis of Intestinal Inflammation in Infectious Diseases, p 351-366. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch19
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Reduced epithelia cell damage in NK-1 receptor-deficient (NK-1R) mice in response to toxin A. Histologic evaluation of toxin A-induced enteritis in wild-type and NK-1R mice. Injection of toxin A to mouse ileum of normal +/+ mice causes acute necroinflammatory damage with epithelial cell destruction and infiltration of the lamina propria with neutrophils (B), compared to buffer injection (A). Buffer-injected ileum of NK-1R shows normal epithelial architecture (C) compared to +/+ mice (A). Toxin A administration to NK-1R mouse ileum shows a dramatic diminution of toxin A-associated histopathologic changes (D) compared to a histopathology section from toxin A-exposed ileum of +/+ mice (B). Original magnification, ×160. (From reference , with permission.)

Citation: Pothoulakis C. 2003. Neuroimmune Interactions and Pathogenesis of Intestinal Inflammation in Infectious Diseases, p 351-366. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch19
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Image of FIGURE 2

toxin A stimulates NTR1 protein expression in rat colon. Rat colonic loops were injected with purified toxin A or buffer and after 2 h colonic tissues were processed for immunohistochemistry using an antibody directed against two N-terminal peptides of NTR1. Toxin A injection resulted in increased NTR1 expression (b) compared to control colon (a). (c) Toxin A-exposed colon incubated with NTR1 antiserum preabsorbed with an excess of the receptor peptides used to generate the antibody shows the complete disappearance of signal. Higher magnification of (d) demonstrates the presence of intense signal on epithelial cells (arrows in b and d) as well as on cells of the lamina propria (arrowhead). Bar, 50 µm. (From reference , with permission.)

Citation: Pothoulakis C. 2003. Neuroimmune Interactions and Pathogenesis of Intestinal Inflammation in Infectious Diseases, p 351-366. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch19
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Intestinal responses regulated by neuroimmune interactions during inflammatory parasitic infection

Citation: Pothoulakis C. 2003. Neuroimmune Interactions and Pathogenesis of Intestinal Inflammation in Infectious Diseases, p 351-366. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch19

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