Lack of galectin-3 alleviates trypanosomiasis-associated anemia of inflammation.
A typical pathological feature associated with experimental African trypanosomiasis (Trypanosoma brucei infection in mice) is anemia of chronic disease (ACD), which is due to a sustained type 1 cytokine-mediated inflammation and hyperactivation of M1 macrophages. Galectin-3 (Gal-3) was amply documented to contribute to the onset and persistence of type 1 inflammatory responses and we herein document that this protein is strongly upregulated during T. brucei infection. We evaluated the involvement of Gal-3 in trypanosomiasis-associated anemia using galectin-3 deficient (Gal3(-/-)) mice. T. brucei infected Gal3(-/-) mice manifested significant lower levels of anemia during infection and survived twice as long as wild type mice. Moreover, such mice showed increased levels of serum IL-10 and reduced liver pathology (as evidenced by lower AST/ALT levels). In addition, there was also an increase in gene expression of iron export genes and a reduced expression of genes, which are associated with accumulation of cellular iron. Our data indicate that Gal-3 is involved in the development of inflammation-associated anemia during African trypanosomiasis, possibly due to a disturbed iron metabolism that in turn may also lead to liver malfunction.
Vankrunkelsven
Ann
A
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium. annvankrunkelsven@yahoo.com
De Ceulaer
Kris
K
Hsu
Daniel
D
Liu
Fu-Tong
FT
De Baetselier
Patrick
P
Stijlemans
Benoît
B
D000410:Alanine Transaminase / Q000235:genetics / Q000378:metabolism; D000740:Anemia; D000818:Animals; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D037502:Galectin 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014346:Trypanosoma brucei brucei / Q000276:immunology* / Q000472:pathogenicity; D014353:Trypanosomiasis, African / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology
D016207:Cytokines; D037502:Galectin 3; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase