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Eosinophil Deficiency Compromises Parasite Survival in Chronic Nematode Infection¹

Valeria Fabre^*, Daniel P. Beiting^2,*, Susan K. Bliss^*, Nebiat G. Gebreselassie^*, Lucille F. Gagliardo^*, Nancy A. Lee, James J. Lee and Judith A. Appleton^3,*

^* James A. Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853; Department of Hematology and Oncology, and Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ 85259

Immune responses elicited by parasitic worms share many features with those of chronic allergy. Eosinophils contribute to the inflammation that occurs in both types of disease, and helminths can be damaged or killed by toxic products released by eosinophils in vitro. Such observations inform the widely held view that eosinophils protect the host against parasitic worms. The mouse is a natural host for Trichinella spiralis, a worm that establishes chronic infection in skeletal muscle. We tested the influence of eosinophils on T. spiralis infection in two mouse strains in which the eosinophil lineage is ablated. Eosinophils were prominent in infiltrates surrounding infected muscle cells of wild-type mice; however, in the absence of eosinophils T. spiralis muscle larvae died in large numbers. Parasite death correlated with enhanced IFN- and decreased IL-4 production. Larval survival improved when mice were treated with inhibitors of inducible NO synthase, implicating the NO pathway in parasite clearance. Thus, the long-standing paradigm of eosinophil toxicity in nematode infection requires reevaluation, as our results suggest that eosinophils may influence the immune response in a manner that would sustain chronic infection and insure worm survival in the host population. Such a mechanism may be deployed by other parasitic worms that depend upon chronic infection for survival.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant AI14490 from the National Institutes of Health (to J.A.A.) and by Grant HL065228 from the National Institutes of Health with additional support from the Mayo Clinic Foundation (to J.J.L. and N.A.L.).

² Current address: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104.

³ Address correspondence and reprint requests to Dr. Judith A. Appleton, James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. E-mail address: jaa2{at}cornell.edu

⁴ Abbreviations used in this paper: NBL, newborn larvae; LPF, low power field; iNOS, inducible NO synthase; AMG, aminoguanidine; dpoi, days post-oral infection; dpi, days postinfection; CLN, cervical lymph node; MLN, mesenteric lymph node; L-NIL, N⁶(2-iminoethyl) L-lysine dihydrochloride.

⁵ The online version of this article contains supplemental material.