MIF contributes to Trypanosoma brucei associated immunopathogenicity development

• Published in: PLoS pathogens Vol. 10; no. 9; p. e1004414
• Main Authors: Stijlemans, Benoît, Leng, Lin, Brys, Lea, Sparkes, Amanda, Vansintjan, Liese, Caljon, Guy, Raes, Geert, Van Den Abbeele, Jan, Van Ginderachter, Jo A, Beschin, Alain, Bucala, Richard, De Baetselier, Patrick
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-09-2014; Public Library of Science (PLoS)
• Subjects: Anemia; Anemia - immunology; Anemia - metabolism; Anemia - parasitology; Anemia - pathology; Animals; Apoptosis - immunology; Biology and Life Sciences; Blotting, Western; Bone Marrow - immunology; Bone Marrow - parasitology; Bone Marrow - pathology; Cells, Cultured; Chronic illnesses; Comparative analysis; Cytokines - genetics; Cytokines - metabolism; Developing countries; Development and progression; Erythrocytes - immunology; Erythrocytes - metabolism; Erythrocytes - parasitology; Erythrocytes - pathology; Experiments; Female; Flow Cytometry; Gene expression; Health aspects; Infections; Intramolecular Oxidoreductases - physiology; Liver - immunology; Liver - parasitology; Liver - pathology; Macrophage Migration-Inhibitory Factors - physiology; Macrophages - immunology; Macrophages - metabolism; Macrophages - parasitology; Macrophages - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes - immunology; Monocytes - metabolism; Monocytes - parasitology; Monocytes - pathology; Neutrophils - immunology; Neutrophils - metabolism; Neutrophils - parasitology; Neutrophils - pathology; Parasites; Parasitic diseases; Population; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Risk factors; RNA, Messenger - genetics; Rodents; Spleen - immunology; Spleen - metabolism; Spleen - parasitology; Spleen - pathology; Trypanosoma brucei; Trypanosoma brucei brucei - pathogenicity; Trypanosomiasis, African - immunology; Trypanosomiasis, African - metabolism; Trypanosomiasis, African - parasitology; Trypanosomiasis, African - pathology
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1004414

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.