Abstract
Inflammatory bowel disease (IBD) in dogs is associated with clinical signs of intestinal dysfunction, as well as abnormal lymphocytic and myeloid cell infiltrates in the small and/or large intestine. Thus, in many respects IBD in dogs resembles IBD in humans. However, the factors that trigger intestinal inflammation in dogs with IBD are not well understood and have been variously attributed to immune responses against dietary antigens or intestinal antigens. Previous studies in humans with IBD have documented increased production of IgG and IgA antibodies specific to intestinal bacteria, and this abnormal immune response has been linked to disease pathogenesis. Therefore, we investigated the humoral immune response against gut bacteria in dogs with IBD, using flow cytometry to quantitate IgG and IgA binding. Studies were also done to investigate the source of these antibodies (locally produced versus systemic production) and whether greater antibody binding to bacteria is associated with increased inflammatory responses. We found that dogs with IBD had significantly higher percentages and overall amounts of IgG bound to their intestinal bacteria compared to healthy dogs. Similarly, significantly higher percentages of bacteria were IgA+ bacteria were also found in dogs with IBD. Serum antibody recognition of gut bacteria was not different between healthy dogs and dogs with IBD, suggesting that anti-bacterial antibodies were primarily produced locally in the gut rather than systemically. Importantly, bacteria in the Actinobacteria phylum and in particular the genus Collinsella had significantly greater levels of antibody binding in dogs with IBD. Based on these findings, we concluded that antibody binding to commensal gut bacteria was significantly increased in dogs with IBD, that particular phyla were preferential targets for gut antibodies, and that anti-bacterial antibody responses may play an important role in regulating gut inflammation.
Highlights
Inflammatory bowel disease (IBD) in dogs is characterized by infiltration of lymphocytes and macrophages into the mucosa and submucosa and clinical signs of GI dysfunction
Humoral immune responses against gut bacteria in IBD dog Competing interests: The authors disclose that an invention disclosure regarding the potential diagnostic utility of the fecal IgG flow cytometric assay has been filed with the Colorado State University technology transfer office with title “Bacterial IgG assay for detection and monitoring of inflammatory bowel disease in companion animals” and the provisional patent application has been filed
We found that macrophages incubated with bacteria from IBD dogs produced significantly greater amounts of TNF-α than macrophages incubated with bacteria from healthy dogs (Fig 5)
Summary
Humoral immune responses against gut bacteria in IBD dog Competing interests: The authors disclose that an invention disclosure regarding the potential diagnostic utility of the fecal IgG flow cytometric assay has been filed with the Colorado State University technology transfer office with title “Bacterial IgG assay for detection and monitoring of inflammatory bowel disease in companion animals” (intervention ID ‘INV19-002’) and the provisional patent application has been filed (application No 62/827,436). This does not alter our adherence to PLOS ONE policies on sharing data and materials. Studies in IBD in humans (e.g., Crohn’s disease, ulcerative colitis) have focused on the role of immune responses targeted to gut bacteria, as opposed to immune responses targeting gut tissues or dietary antigens [9,10,11,12]
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