HOME
Return to Table of Contents
56 EXPOSURE OF THE DEVELOPING IMMUNE SYSTEM TO E COLI DNA AND BACTERIAL SONICATES ENHANCES THE INTESTINAL MUCOSAL RESPONSE TO BACTERIAL ANTIGENS IN LATER LIFE P Bach, F Cheung, D Thiel, B Diederichs, J Ewaschuk, C Arrieta, K Madsen Patients with Crohn's disease (CD) demonstrate a loss of tolerance and a heightened mucosal inflammatory response in the gut toward selected groups of bacterial antigens. Previous studies have suggested that systemic exposure to particular antigens is necessary for the loss of mucosal tolerance to occur, and further, that the time of life that exposure occurs influences the immune response. In addition, it has been shown that specific CpG-DNA motifs act to significantly enhance immune responses. Whether or not systemic immune exposure to native bacterial DNA results in a similar adjunctive effect is unknown.
University of Alberta, Edmonton, Alberta
OBJECTIVE: The objective of this study was to examine the hypothesis that exposure of the developing immune system in neonates to certain bacterial DNA in combination with bacterial protein antigens would trigger a loss of tolerance to gut bacteria that would be maintained in later life.
METHODS: At 3 or 12 wks of age, 129 Sv/Ev mice were injected sc once only with either Clostridium sordelli or Viridans group Streptococci (VGS) protein sonicates ± E coli DNA (50 µg). After 4 wks, mice were sacrificed and small and large intestine removed and cultured for 24 h for measurement of IFN
RESULTS: Colons from mice that had been systemically exposed to C sordelli protein sonicate at 3 wks of age did not have any histological inflammation, but did have significantly increased levels of C sordelli-induced secretion of IFNg and TNFa compared with control mice. In contrast, mice that had been exposed to both E coli DNA and C sordelli sonicate had a substantially enhanced both basal and stimulated cytokine secretion compared with mice that had received C sordelli sonicate. This mucosal response to a systemic bacterial exposure was not universal; however, as mice injected with VGS sonicate did not demonstrate increased basal or stimulated cytokine secretion. Further, the addition of E coli DNA to VGS sonicate did not enhance gut mucosal response to bacterial antigens. E coli DNA injection alone had no effect. Mice that were exposed to C sordelli or VGS ± E coli DNA as adults did not demonstrate an enhanced immune response in later life.
CONCLUSIONS: This data indicates that exposure of the systemic immune system in neonates to certain bacterial DNA in combination with some, but not all, bacterial antigens results in a increased immune response in the gut to normal microflora for several weeks after exposure.