Characterization of central macrophages in Anemia of Inflammation (AI): African trypanosomiasis as a model system
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1
Vrije Universiteit Brussel, VUB, Belgium
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2
Vlaams Instituut voor Biotechnologie, VIB, Laboratory of Myeloid Cell Immunology, MCI, Belgium
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3
Erasmus MC, Department of Cell Biology, Netherlands
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4
Erasmus MC, Department of Immunology, Netherlands
Background: Anemia of Inflammation (AI), or Anemia of Chronic Disease (ACD), is the most prominent form of anemia in hospitalized patients, affecting quality of life and resulting from an imbalance between erythrophagocytosis and erythropoiesis. Multiple mechanisms contribute to its pathogenesis, including iron restriction, direct erythropoietic suppression and shortened erythrocyte survival. A common parameter in AI is a persistent pro-inflammatory immune response of the host, whereby macrophages and their activation state play a key role. In the regulation of erythropoiesis, the enigmatic central macrophages are thought to be essential as part of erythroblastic islands.
Results: By scrutinizing African trypanosomiasis in mice as a model of infectious disease associated with AI, we could discriminate within the F4/80+ER-HR3+ macrophage population 4 distinct subsets (CD11b-/lowLy6C-/low, CD11b-/lowLy6C+, CD11b+Ly6C+Fo-SGL+ and CD11b+Ly6C-/low). Using an in vitro erythropoiesis assay we could establish that CD11b+Ly6C+Fo-SGL+ cells represent the best candidates to function as central macrophages, since these cells are able to aid in the maturation of erythroblasts. Furthermore, they express crucial adhesion molecules (VCAM-1, CD49d, CD169 and CD36) favoring erythroblastic island formation. Moreover, the gene expression levels of crucial iron-homeostasis-associated genes such as CD71, hmox-1, fpn-1 and fhc suggest that this population rather exports iron during infection in contrast to other myeloid cells. Interestingly, by comparing Trypanosome-infected wild-type and mice exhibiting different degrees of anemia, we observed that there was an inverse correlation between the CD11b+Ly6C+Fo-SGL+ population size and anemia development. Therefore, this population requires further investigation to unravel its exact role in AI development.
Acknowledgements
I would like to acknowledge all the technical staff that contributed to this work or gave logistic support: Ella Omasta, Marie-Thérèse Detobel, Maria Slazak, Yvon Elkrim, Lea Brys, Nadia Abou, Eddy Vercauteren
References
Weiss G (Iron metabolism in the anemia of chronic disease. Biochim Biophys Acta 1790:682-693.2009).
Stijlemans B, Vankrunkelsven A, Caljon G, Bockstal V, Guilliams M, Bosschaerts T, Beschin A, Raes G, Magez S, De Baetselier P (The central role of macrophages in trypanosomiasis-associated anemia: rationale for therapeutical approaches. Endocr Metab Immune Disord Drug Targets 10:71-82.2010).
Keywords:
macrophage,
Anemia of Inflammation,
Anemia of Chronic Disease,
Erythropoiesis,
Erythroblastic island
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Vansintjan
L,
Stijlemans
B,
Philipsen
S,
Leenen
PJ and
De Baetselier
P
(2013). Characterization of central macrophages in Anemia of Inflammation (AI): African trypanosomiasis as a model system.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01099
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Received:
10 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Ms. Liese Vansintjan, Vrije Universiteit Brussel, VUB, Brussels, Belgium, liese.vansintjan@vub.ac.be