Immunohistochemical characterization of gastrointestinal macrophages/phagocytes in dogs with inflammatory bowel disease (IBD) and non-IBD dogs

Intestinal Mϕ play a pivotal role in the maintenance of gut homeostasis, but can also contribute to inflammation such as inflammatory bowel disease (IBD). In contrast to human tissues, little is known about phenotypes of Mϕ in the canine gastrointestinal tract. Therefore, an immunohistochemical study was performed using Abs against Mϕ-associated molecules (Cluster of differentiation (CD)64, CD163, CD204, ionized calcium-binding adaptor molecule 1, L1 Ag, and MHC II) on stomach, duodenum, jejunum, ileum and colon from non-IBD dogs. In addition, marker-expression in the stomach, duodenum and colon of the non-IBD dogs was compared to that in dogs with IBD. Results revealed predominance of resident Mϕ displaying an anti-inflammatory phenotype represented by expression of CD163 as well as CD204 in the gut of non-IBD dogs with high Mϕ numbers especially present in the small intestinal villus area. Compared to non-IBD tissue counterparts, stomach, duodenum, and colon from dogs with IBD showed reduced Mϕ numbers with the exception of slightly increased numbers of CD64+ Mϕ. Correlation analyses between marker-expression of Mϕ and the Canine Inflammatory Bowel Disease Activity Index as well as histological scores failed to reveal relevant relationships. The present study provides evidence of the canine steady state gastrointestinal tract being dominated by Mϕ with anti-inflammatory properties maintaining gut homeostasis. A significant reduction in these resident Mϕ may reflect disturbances in homeostatic capacity that could contribute to the development of canine IBD. In contrast to human IBD and murine disease models, infiltration of pro-inflammatory Mϕ does not significantly contribute to the inflammatory process of canine IBD, which may illustrate possible species-specific differences in IBD pathogenesis.