Those authors hypothesized that a state of unresponsiveness to th

Those authors hypothesized that a state of unresponsiveness to the endogenous microflora may be apparent only after a transient mucosal immune response has occurred [24]. The response to bacteria and bacterial antigens we observed in our experiment might be elevated due in part to a transient unphysiological high load of bacteria in the axenic mice; however, it might mimic a response that occurs on a frequent basis, albeit less pronounced,

whenever a new bacterial strain is introduced in the intestinal lumen. The changes in the intestinal milieu with regard to cytokine and chemokine secretion as well as expression of cell surface antigens may instigate the generation of immune-regulatory cells. A crucial role for the presence of a microflora in the induction of regulatory T cells has been demonstrated in a murine transfer model of colitis [25]. Protective T cells showed reduced efficacy in preventing colitis development and demonstrated buy 3-MA reduced release of IL-10 and IFN-γ see more when derived from axenic mice as opposed to those derived from conventionally housed mice. While we did not detect a significant increase in systemic T cells with a common

regulatory phenotype, such as CD25-positive T cells, we cannot exclude the generation of a specific population of cells with regulatory function in mucosal tissues and/or systemically. The increased CD11b-positive leucocyte population may be involved in the suppression of activated T cell responses. Myeloid-derived suppressor cells with a CD11b-positive, Gr-1-positive phenotype and immunosuppressive function have been described and have been implicated in Farnesyltransferase the protection of T cell-mediated chronic enterocolitis [26,27]. We have demonstrated previously a similar rapid onset of proinflammatory cytokine and intestinal injury in adult axenic IL-10 gene-deficient mice following colonization with commensal faecal flora [8]. A similar uncontrolled proinflammatory cytokine response to commensal bacterial antigens has also been found to play a crucial role in the human leucocyte antigen-B27 (HLA-B27) transgenic rat

colitis model [28]. Our results demonstrate for the first time that bacterial colonization in wild-type mice initially triggers a similar proinflammatory immune response, causing temporary intestinal inflammation. Endogenous bacterial antigens are treated as ‘foreign’ and stimulate an antigen-specific systemic immune response. However, in contrast to colitis susceptible rodents, wild-type mice are able to down-regulate the initial proinflammatory immune response and establish mucosal as well as systemic tolerance. Acquisition of immunological homeostasis appears to follow a defined inflammatory response pattern when first exposed to faecal bacteria and antigens, which probably plays an important role in the induction of tolerance to the endogenous microflora.

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