MIF Contributes to Trypanosoma brucei Associated Immunopathogenicity Development

PLoS Pathogens

Richard Bucala¹  Amanda Sparkes¹  Benoît Stijlemans¹  Guy Caljon¹  Jan Van Den Abbeele¹  Lea Brys²  Liese Vansintjan³  Lin Leng³  Geert Raes³  Patrick De Baetselier³  Jo A. Van Ginderachter³  Alain Beschin⁴ 

[1] Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium;Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America;Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium;Unit of Veterinary Protozoology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium

关键词: Trypanosoma brucei gambiense;    Neutrophils;    Anemia;    Inflammation;    Monocytes;    Pathogenesis;    Bone marrow cells;    Trypanosoma;   

DOI  :  10.1371/journal.ppat.1004414

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 Ly6Chigh 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.

【 授权许可】

CC BY