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United States Department of Agriculture

Agricultural Research Service

Title: TH2-INDUCING PARASITE INFECTION LEADS TO THE PRODUCTION OF IL-4 AND TISSUE ACCUMULATION OF BASOPHILS)

Author
item Min, Booki
item Prout, Melania
item Hu-li, Jame
item Zhu, Jinfang
item Jankovic, Dragana
item Morgan, Ellen
item Urban, Joseph
item Dvorak, Ann
item Finkelman, Fred
item Legros, Graham

Submitted to: Journal of Experimental Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/10/2004
Publication Date: 8/16/2004
Citation: Min, B., Prout, M., Hu-Li, J., Zhu, J., Jankovic, D., Morgan, E., Urban Jr, J.F., Dvorak, A., Finkelman, F., Legros, G. 2004. Th2-inducing parasite infection leads to the production of IL-4 and tissue accumulation of basophils. Journal of Experimental Medicine. 200:507-517 (2004)

Interpretive Summary: Components of the type 2 immune response mediate host protection against worm parasites. These infections have major impact on efficient production of healthy animals and affect the general health of children in many less developed countries worldwide. A central molecular in activation of this response is a protein messenger molecule called IL-4 that primes lymphocytes to become Th2 cells which are key cellular regulators of protection. Specific aspects of the parasite that trigger cells to produce IL-4 through cell differentiation and activation have not been conclusively identified. The worm acts as adjuvant to promote naïve cells to differentiate into IL-4 producing cells during the course of infection. We have found that these parasites have a potent adjuvant effect on cells in the bone marrow that cause them to produce IL-4 and prime the animal for development of a type 2 response. Since this is the first definite target for early IL-4 production, the information can be used to more efficiently regulate the response to enhance resistance or reduce the potential for negative side effects of an unregulated response. This information will be of interest to investigators that study protective immunity to worm infections.

Technical Abstract: Using mice in which the eGfp gene replaced the first exon of the Il4 gene (G4 mice), we examined production of IL-4 during infection of intestinal nematode N. brasiliensis (Nb). Nb infection induced GFPpos cells that were FceRIpos, CD49bbright, c-kitneg and Gr1neg. These cells had lobulated nuclei and granules characteristic of basophils. They were found mainly in the liver and lung, to a lesser degree in spleen, but not in lymph nodes. Although some of liver basophils from naïve mice express GFP, Nb infection enhanced GFP expression and increased the number of tissue basophils. Similar basophil GFP expression was found in infected Stat6-/- mice. Basophils did not increase in number in infected in Rag2-/- mice; reconstitution with CD4 T cells allowed basophil accummulation, indicating that CD4 T cells can direct both tissue migration of basophils and enhanced cytokine production. Cytokine production is immunoglobulin-independent and only partially dependent on IL-3. Infection with a parasite that induces a 'Th2-type response' results in accumulation of tissue basophils and these cells, stimulated by non-FcR crosslinking mechanism, are a principal source of IL-4.

Last Modified: 8/24/2016
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