Scrutinizing the mechanisms underlying the induction of anemia of inflammation through GPI-mediated modulation of macrophage activation in a model of African trypanosomiasis.
In animal trypanosomiasis the severity of infection is reflected by the degree of anemia which resembles anemia of inflammation, involving a skewed iron homeostasis leading to iron accumulation within the reticuloendothelial system. Myeloid cells (M cells) have been implicated in the induction and maintenance of this type of anemia and modulation of M cells through the main trypanosome-derived glycosylphosphatidylinositol (GPI)-anchor could attenuate both anemia and trypano-susceptibility in Trypanosoma brucei-infected mice. Herein the GPI-based treatment, allowing a straightforward comparison between trypanotolerance and susceptibility in T. brucei-infected C57Bl/6 mice, was further adopted to scrutinize mechanisms/pathways underlying trypanosome-elicited anemia. Hereby, the following interlinkable observations were made in GPI-based treated (GBT) T. brucei-infected mice: (i) a reduced inflammatory cytokine production and increased IL-10 production associated with alleviation of anemia and restoration of serum iron levels, (ii) a shift in increased liver expression of iron storage towards iron export genes, (iii) increased erythropoiesis in the bone marrow and extramedullar sites (spleen) probably reflecting a normalized iron homeostasis and availability. Collectively, our results demonstrate that reprogramming macrophages towards an anti-inflammatory state alleviates anemia of inflammation by normalizing iron homeostasis and restoring erythropoiesis.
Stijlemans
Benoît
B
Department of Molecular and Cellular Interactions, VIB, 1050 Brussel, Belgium. bstijlem@vub.ac.be
Vankrunkelsven
Ann
A
Brys
Lea
L
Raes
Geert
G
Magez
Stefan
S
De Baetselier
Patrick
P
D000740:Anemia / Q000209:etiology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000276:immunology*; D006801:Humans; D007249:Inflammation; D007501:Iron / Q000097:blood; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D044967:Serum / Q000737:chemistry; D014346:Trypanosoma brucei brucei / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000150:complications* / Q000276:immunology*
D016207:Cytokines; D017261:Glycosylphosphatidylinositols; D007501:Iron