title: MIF contributes to Trypanosoma brucei associated immunopathogenicity development.
abstract: African trypanosomiasis is a chronic debilitating disease affecting the health and economic well-being of many people in developing countries. The pathogenicity associated with this disease involves a persistent inflammatory response, whereby M1-type myeloid cells, including Ly6C(high) inflammatory monocytes, are centrally implicated. A comparative gene analysis between trypanosusceptible and trypanotolerant animals identified MIF (macrophage migrating inhibitory factor) as an important pathogenic candidate molecule. Using MIF-deficient mice and anti-MIF antibody treated mice, we show that MIF mediates the pathogenic inflammatory immune response and increases the recruitment of inflammatory monocytes and neutrophils to contribute to liver injury in Trypanosoma brucei infected mice. Moreover, neutrophil-derived MIF contributed more significantly than monocyte-derived MIF to increased pathogenic liver TNF production and liver injury during trypanosome infection. MIF deficient animals also featured limited anemia, coinciding with increased iron bio-availability, improved erythropoiesis and reduced RBC clearance during the chronic phase of infection. Our data suggest that MIF promotes the most prominent pathological features of experimental trypanosome infections (i.e. anemia and liver injury), and prompt considering MIF as a novel target for treatment of trypanosomiasis-associated immunopathogenicity.
authors.affiliation: Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium; Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium.
authors.forename: Benoît
authors.initials: B
authors.lastname: Stijlemans
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Lin
authors.initials: L
authors.lastname: Leng
authors.affiliation: Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium; Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium.
authors.forename: Lea
authors.initials: L
authors.lastname: Brys
authors.affiliation: Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium; Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium.
authors.forename: Amanda
authors.initials: A
authors.lastname: Sparkes
authors.affiliation: Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium; Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium.
authors.forename: Liese
authors.initials: L
authors.lastname: Vansintjan
authors.affiliation: Unit of Veterinary Protozoology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Caljon
authors.affiliation: Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium; Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Raes
authors.affiliation: Unit of Veterinary Protozoology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van Den Abbeele
authors.affiliation: Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium; Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium.
authors.forename: Jo A
authors.initials: JA
authors.lastname: Van Ginderachter
authors.affiliation: Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium; Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Beschin
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.affiliation: Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium; Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
mesh_terms: D000740:Anemia / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D019746:Intramolecular Oxidoreductases / Q000502:physiology*; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000502:physiology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D014346:Trypanosoma brucei brucei / Q000472:pathogenicity*; D014353:Trypanosomiasis, African / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology
chemical_list: D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse