MIF contributes to Trypanosoma brucei associated immunopathogenicity development.

Benoit Stijlemans, Lin Leng, Lea Brys, Amanda Sparkes, Liese Vansintjan, Guy Caljon, Geert Raes, Jan Van Den Abbeele, Jo Van Ginderachter, Alain Beschin, Richard Bucala, Patrick De Baetselier

Onderzoeksoutput: Articlepeer review

37 Citaten (Scopus)

Samenvatting

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.
Originele taal-2English
Artikelnummere1004414
Aantal pagina's13
TijdschriftPLoS Pathog.
Volume10
DOI's
StatusPublished - 25 sep 2014

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