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Infection and Immunity, December 1998, p. 5955-5963, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Filarial Nematode Parasites Secrete a Homologue of the Human Cytokine Macrophage Migration Inhibitory Factor

Diana V. Pastrana,1 Nithyakalyani Raghavan,1 Peter FitzGerald,2 Stephen W. Eisinger,1 Christine Metz,3 Richard Bucala,3 Robert P. Schleimer,4 Carol Bickel,4 and Alan L. Scott1,*

Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 212051; Division of Computer Research and Technology, National Institutes of Health, Bethesda, Maryland 208922; Department of Clinical Immunology, Asthma and Allergy Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland 212244; and The Picower Institute for Medical Research, Manhasset, New York 110303

Received 7 May 1998/Returned for modification 19 June 1998/Accepted 10 August 1998

Filarial nematode parasites establish long-term chronic infections in the context of an antiparasite immunity that is strongly biased toward a Th2 response. The mechanisms that lead to this Th2 bias toward filarial antigens are not clear, but one possibility is that the parasites produce molecules that have the capacity to proactively modify their immunological environment. Here we report that filarial parasites of humans secrete a homologue of the human proinflammatory cytokine macrophage migration inhibitory factor (MIF) that has the capability of modifying the activity of human monocytes/macrophages. A cDNA clone isolated from a Brugia malayi infective-stage larva expression library encoded a 12.5-kDa protein product (Bm-MIF) with 42% identity to human and murine MIF. MIF homologues were also found to be expressed in the related filarial species Wuchereria bancrofti and Onchocerca volvulus. Bm-mif was transcribed by adult and larval parasites, and the protein product was found in somatic extracts and in the parasite's excretory-secretory products. Immunohistocytochemistry revealed that Bm-MIF was localized to cells of the hypodermis/lateral chord, the uterine wall, and larvae developing in utero. Unexpectedly, the activities of recombinant Bm-MIF and human MIF on human monocytes/macrophages were found to be similar. When placed with monocytes/macrophages in a cell migration assay, Bm-MIF inhibited random migration. When placed away from cells, Bm-MIF induced an increase in monocyte/macrophage migration that was specifically inhibited by neutralizing anti-Bm-MIF antibodies. Bm-MIF is the first demonstration that helminth parasites produce cytokine homologues that have the potential to modify host immune responses to promote parasite survival.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, 615 North Wolfe St., Baltimore, MD 21205. Phone: (410) 955-3442. Fax: (410) 955-0105. E-mail: ascott{at}jhsph.edu.

Infection and Immunity, December 1998, p. 5955-5963, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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