Document Detail


Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor.
MedLine Citation:
PMID:  9826378     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
D V Pastrana; N Raghavan; P FitzGerald; S W Eisinger; C Metz; R Bucala; R P Schleimer; C Bickel; A L Scott
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Infection and immunity     Volume:  66     ISSN:  0019-9567     ISO Abbreviation:  Infect. Immun.     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1998-12-24     Completed Date:  1998-12-24     Revised Date:  2014-06-20    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5955-63     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AF040629;  U88035
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Brugia malayi / genetics
Cell Movement
Female
Filarioidea / genetics,  metabolism*
Gerbillinae
Humans
Macrophage Migration-Inhibitory Factors / genetics,  pharmacology,  secretion*
Macrophages / drug effects
Male
Molecular Sequence Data
Monocytes / drug effects
Onchocerca volvulus / genetics
Sequence Homology, Amino Acid
Wuchereria bancrofti / genetics
Grant Support
ID/Acronym/Agency:
AI-02642/AI/NIAID NIH HHS; AI-29411/AI/NIAID NIH HHS; T32 AI007417/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Macrophage Migration-Inhibitory Factors
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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