Location: Diet, Genomics and Immunology LaboratoryTitle: Heligmosomoides induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut Tcell responses) Author
Submitted to: Journal of Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 7/27/2012
Publication Date: 9/1/2012
Citation: Blum, A.M., Hang, L., Setiawan, T., Urban Jr, J.F., Stoyanoff, K., Leung, J., Weinstock, J.V. 2012. Heligmosomoides induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut Tcell responses. Journal of Immunology. Sept 1:189(5):2512-2520. Interpretive Summary: Helminth (worm) parasites can modulate local inflammation at mucosal surfaces including the intestine and lungs. The mechanisms are largely speculative, but it is clear that regulatory cells and cell products contribute to this response. Understanding worm-induced regulation would help design strategies to effectively eliminate harmful worm infections or utilize their anti-inflammatory properties to modulate disease in livestock and humans. This study used an experimental model of inflammatory bowel disease (IBD) to induce inflammation in the intestine and studied the role that worm infection played in modulating the response. It was observed that the worm induced dendritic cells (DC) in the intestine that could transfer the modulating effects to naïve hosts and prevent the onset of IBD. These results provide a target host cell responsible for the modulating effects of the worm and should generate strategies to regulate the activity of DCs, including changes in diet that could modulate inflammation at mucosal surfaces. The information is important to researchers that study the control of infectious diseases in humans and livestock, and the relationship between parasitic infection and inflammation.
Technical Abstract: Immunological diseases like inflammatory bowel disease (IBD) are infrequent in less developed countries possibly because helminths provide protection by modulating host immunity. In IBD murine models, the helminth Heligmosomoides bakeri (Hb) prevents colitis. It was determined if Hb mediated IBD protection by altering DC function. We used a Rag IBD model where animals were reconstituted with IL10-/- T cells making them susceptible to IBD and with OVA antigen-responsive OT2 T cells allowing study of a gut antigenic response. Intestinal DC from Hb-infected Rag mice added to lamina propria mononuclear cells (LPMC) isolated from colitic animals blocked OVA IFNg/IL17 responses in vitro through direct contact with the inflammatory LPMC. Transfer of DC from Hb-infected mice into Rag mice reconstituted with IL10-/- T cells protected animals from IBD, and LPMC from these mice lost OVA responsiveness. After DC transfer, OT2 T cells populated the intestines normally. However, the OT2 T cells were rendered antigen-nonresponsive through regulatory action of LPMC non-T cells. Thus, Hb modulates intestinal DC function, rendering them tolerogenic. This appears to be an important mechanism through which Hb suppresses colitis. IFNg and IL17 are colitogenic. The capacity of these DC to block a gut antigen-specific IFNg/IL17 T cell response also is significant.