Commensal bacteria exacerbate intestinal inflammation but are not essential for the development of murine ileitis.

Abstract

The pathogenesis of Crohn's disease has been associated with a dysregulated response of the mucosal immune system against intraluminal Ags of bacterial origin. In this study, we have investigated the effects of germfree (GF) conditions in the SAMP1/YitFc murine model of Crohn's disease-like ileitis. We show that the bacterial flora is not essential for ileitis induction, because GF SAMP1/YitFc mice develop chronic ileitis. However, compared with disease in specific pathogen-free (SPF) mice, ileitis in GF mice is significantly attenuated, and is associated with delayed lymphocytic infiltration and defective mucosal expression of Th2 cytokines. In addition, we demonstrate that stimulation with purified fecal Ags from SPF, but not GF mice leads to the generation of IL-4-secreting effector lymphocytes. This result suggests that commensal bacteria drive Th2 responses characteristic of the chronic phase of SAMP1/YitFc ileitis. Finally, adoptive transfer of CD4-positive cells from GF, but not SPF mice induces severe colitis in SCID recipients. These effects were associated with a decreased frequency of CD4(+)CD25(+)Foxp3(+) T cells in the mesenteric lymph nodes of GF mice compared with SPF mice, as well as lower relative gene expression of Foxp3 in CD4(+)CD25(+) T cells in GF mice. It is therefore apparent that, in the absence of live intraluminal bacteria, the regulatory component of the mucosal immune system is compromised. All together, our results indicate that in SAMP1/YitFc mice, bacterial flora exacerbates intestinal inflammation, but is not essential for the generation of the chronic ileitis that is characteristic of these mice.

• Authors: Giorgos Bamias, Akira Okazawa, Jesus Rivera-Nieves, Kristen O Arseneau, Sarah A De La Rue, Theresa T Pizarro, Fabio Cominelli
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 178 Issue 3 Pg. 1809-18 (Feb 01 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17237431 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Forkhead Transcription Factors
• Foxp3 protein, mouse

Topics

• Adoptive Transfer
• Animals
• Bacteria (pathogenicity)
• CD4-Positive T-Lymphocytes (transplantation)
• Chemotaxis, Leukocyte
• Crohn Disease
• Cytokines
• Forkhead Transcription Factors (genetics)
• Ileitis (etiology, pathology)
• Inflammation (microbiology)
• Intestines (microbiology, pathology)
• Lymph Nodes
• Mice
• Mice, SCID
• Mucous Membrane (immunology)
• T-Lymphocytes, Regulatory (cytology)
• Th2 Cells