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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
A critical role for the host mediator macrophage migration inhibitory factor in the pathogenesis of malarial anemia
Journal of Experimental Medicine, Volume 203, No. 5, Year 2006
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Description
The pathogenesis of malarial anemia is multifactorial, and the mechanisms responsible for its high mortality are poorly understood. Studies indicate that host mediators produced during malaria infection may suppress erythroid progenitor development (Miller, K.L., J.C. Schooley, K.L. Smith, B. Kullgren, L.J. Mahlmann, and P.H. Silverman. 1989. Exp. Hematol. 17:379-385; Yap, G.S., and M.M. Stevenson. 1991. Ann. NY Acad. Sci. 628:279-281). We describe an intrinsic role for macrophage migration inhibitory factor (MIF) in the development of the anemic complications and bone marrow suppression that are associated with malaria infection. At concentrations found in the circulation of malaria-infected patients, MIF suppressed erythropoietin-dependent erythroid colony formation. MIF synergized with tumor necrosis factor and γ interferon, which are known antagonists of hematopoiesis, even when these cytokines were present in subinhibitory concentrations. MIF inhibited erythroid differentiation and hemoglobin production, and it antagonized the pattern of mitogen-activated protein kinase phosphorylation that normally occurs during erythroid progenitor differentiation. Infection of MIF knockout mice with Plasmodium chabaudi resulted in less severe anemia, improved erythroid progenitor development, and increased survival compared with wild-type controls. We also found that human mononuclear cells carrying highly expressed MIF alleles produced more MIF when stimulated with the malarial product hemozoin compared with cells carrying low expression MIF alleles. These data suggest that polymorphisms at the MIF locus may influence the levels of MIF produced in the innate response to malaria infection and the likelihood of anemic complications. JEM © The Rockefeller University Press.
Authors & Co-Authors
McDevitt, Michael A.
United States, Baltimore
Johns Hopkins University
Xie, Jianlin
United States, Manhasset
Feinstein Institute for Medical Research
United States, Chicago
Pritzker School of Medicine
Shanmugasundaram, Ganapathy
United States, Baltimore
Johns Hopkins University
Griffith, Jason
United States, New Haven
Yale University
Liu, Aihua
United States, New Haven
Yale University
McDonald, Courtney
United States, New Haven
Yale University
Thuma, Philip E.
Zambia
Macha Malaria Research Institute
Gordeuk, Victor R.
United States, Washington, D.c.
Howard University
United States, Washington, D.c.
The Center for Sickle Cell Disease
Metz, Christine Noel
United States, Manhasset
Feinstein Institute for Medical Research
Mitchell, Robert A.
United States, Louisville
University of Louisville
Keefer, Jeffrey Renn
United States, Baltimore
Johns Hopkins University
David, John R.
United States, Boston
Harvard T.h. Chan School of Public Health
Leng, Lin
United States, New Haven
Yale University
Bucala, Richard John
United States, New Haven
Yale University
Statistics
Citations: 141
Authors: 14
Affiliations: 9
Identifiers
Doi:
10.1084/jem.20052398
ISSN:
00221007
e-ISSN:
00221007
Research Areas
Cancer
Infectious Diseases