Crucial Role of MIF in Trypanosomiasis-elicited Inflammation-associated Immunopathology.

Benoit Stijlemans, Lin Leng, LEA BRYS, Amanda Sparkes, Geert Raes, Richard Bucala, Patrick De Baetselier

Onderzoeksoutput: Meeting abstract (Book)

Samenvatting

The major pathological parameter in African trypanosomiasis is anemia of chronic disease (ACD),
whereby iron homeostasis is skewed towards iron accumulation within the reticuloendothelial system.
Hereby, a sustained type-1 cytokine-mediated inflammation and hyperactivation of myeloid cells
contributes to the development of trypanosomiasis-associated immunopathology (anemia and liver injury).
Furthermore, the polarization of myeloid (M) cells into distinct activation states (M1, M2) may contribute to
trypanosusceptibility or tolerance. Reprogramming macrophages from M1 towards M2 alleviates ACD and
normalizes iron homeostasis and erythropoiesis. A comparative gene analysis between a
trypanosusceptible and tolerant model identified MIF (macrophage migrating inhibitory factor) as a
potential candidate involved in inflammation-associated pathology.
The contribution of MIF in inflammation-associated pathology was evaluated using MIF-deficient mice
(MIF-/-) as well an anti-MIF neutralising antibody. In addition, a comparative gene expression study,
focussing on genes involved in iron homeostasis and erythropoiesis, was performed using myeloid cells
from wild-type and MIF-/- mice. The results revealed that MIF plays an important role in maintaining a
prominent pro-inflammatory immune response. Furthermore, trypanosome-infected MIF-/- mice exhibited
reduced anemia development which coincided with a restored iron-homeostasis and an increased
erythropoiesis compared to wild-type mice. Besides, MIF deficiency resulted in reduced liver injury as
evidenced by serum AST/ALT levels, which was associated with reduced infiltration of inflammatory
(CD11b+
Ly6chigh+) cells expressing CD74, i.e. the cell surface MIF receptor mediating MIF's inflammatory
and proliferative responses.
Therefore, MIF plays a crucial role in trypanosomiasis-elicited inflammation-associated immunopathology.
Hence, targeting the MIF/CD74 axis might be an attractive approach to block inflammation-associated
pathologies.
Originele taal-2English
TitelEMDS Erlangen
StatusPublished - 10 dec 2013
Evenement27th Annual Conference of the European Macrophage and Dendritic Cell Society (EMDS) - Erlangen, Germany
Duur: 10 okt 2013 → …

Conference

Conference27th Annual Conference of the European Macrophage and Dendritic Cell Society (EMDS)
Land/RegioGermany
StadErlangen
Periode10/10/13 → …

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