Neonatal exposure to fecal antigens reduces intestinal inflammation
Corresponding Author
Beate C. Sydora PhD
Center of Excellence for Gastrointestinal Inflammation and Immunity Research, Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Center of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), Division of Gastroenterology, Department of Medicine, University of Alberta, 7142D KGR Building, Edmonton, Alberta, Canada T6G 2X8Search for more papers by this authorSarah M. McFarlane
Center of Excellence for Gastrointestinal Inflammation and Immunity Research, Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorJason S. G. Doyle MD
Department of Laboratory Medicine and Pathology, Vernon Jubilee Hospital, Vernon, British Columbia, Canada
Search for more papers by this authorRichard N. Fedorak MD
Center of Excellence for Gastrointestinal Inflammation and Immunity Research, Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorCorresponding Author
Beate C. Sydora PhD
Center of Excellence for Gastrointestinal Inflammation and Immunity Research, Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Center of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), Division of Gastroenterology, Department of Medicine, University of Alberta, 7142D KGR Building, Edmonton, Alberta, Canada T6G 2X8Search for more papers by this authorSarah M. McFarlane
Center of Excellence for Gastrointestinal Inflammation and Immunity Research, Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorJason S. G. Doyle MD
Department of Laboratory Medicine and Pathology, Vernon Jubilee Hospital, Vernon, British Columbia, Canada
Search for more papers by this authorRichard N. Fedorak MD
Center of Excellence for Gastrointestinal Inflammation and Immunity Research, Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorAbstract
Background:
A role for bacterial antigens in the pathogenesis of inflammatory bowel disease (IBD) has been established in enhanced humoral and cellular immune response to ubiquitous antigens of the enteric flora. However, we have recently shown that bacterial antigens in the absence of live bacteria cannot initiate an intestinal inflammation in IBD-prone interleukin (IL)-10 gene-deficient mice. The objective was to investigate whether neonatal exposure to antigens of their own endogenous flora can tolerize mice to bacterial antigens.
Methods:
IL-10 gene-deficient neonates were injected intraperitoneally within 72 hours of birth with a sterile solution of bacterial lysates prepared from fecal material of either conventionally raised mice (contains bacterial antigens) or axenic mice (lacks bacterial antigens). The onset of intestinal inflammation was monitored as the appearance of occult blood in the stool in weekly hemoccult analysis. Mice were sacrificed between age 15 and 19 weeks and tested for histopathologic injury, intestinal inflammation, and systemic response to bacterial antigens.
Results:
In mice neonatally exposed to bacterial antigens the onset of intestinal inflammation was delayed and the incidence of histopathologic injury at age 18 weeks was reduced. In addition, mice injected with lysates from conventionally raised mice exhibited decreased release of proinflammatory cytokines (interferon gamma [IFN-γ] and IL-17) in intestinal tissue and demonstrated reduced bacteria-stimulated systemic responses when compared to mice injected with lysates derived from bacteria-free, axenic mice.
Conclusions:
Neonatal intraperitoneal injection of antigens from the commensal flora causes long-lasting changes in systemic and mucosal immune responses resulting in delayed onset of intestinal inflammation and injury in IBD-prone IL-10 gene-deficient mice. (Inflamm Bowel Dis 2011;)
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
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| IBD_21453_sm_suppinfofigure1.tif1.8 MB | Supporting Information Figure 1 |
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