Submitted to: Journal of Experimental Medicine
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/7/2009
Publication Date: 12/21/2009
Citation: Herbert, D.R., Yang, J.Q., Hogan, S.P., Groschwitz, K., Khodoun, M., Munitz, A., Orekov, T., Perkins, C., Wang, Q., Brombacher, F., Urban Jr, J.F., Rothenberg, M.E., Finkelman, F.D. 2009. Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection. Journal of Experimental Medicine. 206(13):2947-2957. Interpretive Summary: Parasitic infections have been used to model localized allergic reactions in the intestine because of the physiological and immunological similarity to the response to food allergens. Understanding the nature of this response to parasites is likely to provide targets to control unregulated allergic disease in the intestine. The current study demonstrates that there is an identifiable pattern in the host (the infected individual) that is activated by parasitic infection, but the effectiveness of getting rid of the parasite (parasite clearance) is dependent on only certain components of the total response in the host. Clearance of two worm parasites that feed on the contents of the intestine is blocked by a product called RELMB that binds to the parasite and interferes with its feeding behavior in the gut. This is a specific protein made by the host that is also important in local intestinal responses to allergens. Another worm that directly invades the epithelial tissue of the intestine, however, is not affected by RELMB but is controlled by other aspects of the immune response. These results suggest that physiological changes in the intestine to other stimuli like food allergens also induce identifiable patterned responses that are unrelated to the specific response to the presence of the food allergen. This work will be important to scientists and clinicians interested in the regulation and control of intestinal infectious and allergic diseases that could also include dietary modifications that reduce the intensity of the allergic response.
Technical Abstract: IL-4 and IL-13 protect against parasitic helminths, but little is known about the mechanism of host protection. We show that IL-4/IL-13 confer immunity against worms by inducing intestinal epithelial cells (IEC) to differentiate into goblet cells that secrete resistin-like molecule beta (RELMB). RELMB is essential for normal, spontaneous expulsion and IL-4-induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, both worms that live in the intestinal lumen, but does not contribute to immunity against Trichinella spiralis, which lives within intestinal epithelium. RELMB acts directly on adult worms to reduce fecundity and prevent ability to feed on host tissues without promoting TH2 cytokine production, alternative macrophage activation, mast cell responses, or increased gut permeability.