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Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor.
Infect Immun. 1998 Dec; 66(12):5955-63.II

Abstract

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.

Authors+Show Affiliations

Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9826378

Citation

Pastrana, D V., et al. "Filarial Nematode Parasites Secrete a Homologue of the Human Cytokine Macrophage Migration Inhibitory Factor." Infection and Immunity, vol. 66, no. 12, 1998, pp. 5955-63.
Pastrana DV, Raghavan N, FitzGerald P, et al. Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor. Infect Immun. 1998;66(12):5955-63.
Pastrana, D. V., Raghavan, N., FitzGerald, P., Eisinger, S. W., Metz, C., Bucala, R., Schleimer, R. P., Bickel, C., & Scott, A. L. (1998). Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor. Infection and Immunity, 66(12), 5955-63.
Pastrana DV, et al. Filarial Nematode Parasites Secrete a Homologue of the Human Cytokine Macrophage Migration Inhibitory Factor. Infect Immun. 1998;66(12):5955-63. PubMed PMID: 9826378.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor. AU - Pastrana,D V, AU - Raghavan,N, AU - FitzGerald,P, AU - Eisinger,S W, AU - Metz,C, AU - Bucala,R, AU - Schleimer,R P, AU - Bickel,C, AU - Scott,A L, PY - 1998/11/24/pubmed PY - 1998/11/24/medline PY - 1998/11/24/entrez SP - 5955 EP - 63 JF - Infection and immunity JO - Infect Immun VL - 66 IS - 12 N2 - 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. SN - 0019-9567 UR - https://www.unboundmedicine.com/medline/citation/9826378/Filarial_nematode_parasites_secrete_a_homologue_of_the_human_cytokine_macrophage_migration_inhibitory_factor_ DB - PRIME DP - Unbound Medicine ER -