Patrick De Baetselier

Vrije Universiteit Brussel, Bruxelles, Brussels Capital, Belgium

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Publications (336)1555.61 Total impact

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    ABSTRACT: Tumor-associated macrophages (TAMs) constitute a major component of the stroma of solid tumors, encompassing distinct subpopulations with different characteristics and functions. We aim to identify M2-oriented tumor-supporting macrophages within the tumor microenvironment as indicators of cancer progression and prognosis, using PET imaging. This can be realized by designing Fluor-18 labeled camelid single-domain antibody fragments (sdAbs) specifically targeting the macrophage mannose receptor (MMR), which has been identified as an important biomarker on this cell population. Cross-reactive anti-MMR sdAbs were generated after immunization of an alpaca with the extracellular domains of both human and mouse MMR. The lead binder was chosen based on comparisons of binding affinity and in vivo pharmacokinetics. The PET-tracer [(18)F]-FB-anti-MMR sdAb was developed using the prosthetic group N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]-SFB), and its biodistribution, tumor targeting potential and specificity in terms of macrophage and MMR targeting was evaluated in preclinical mouse tumor models. Four sdAbs were selected after affinity screening but only 2 were found to be cross-reactive for human and mouse MMR. The lead anti-MMR 3.49 sdAb, bearing an affinity of 12 and 1.8 nM for mouse and human MMR; respectively, was chosen for its favorable in vivo biodistribution profile and tumor targeting capacity. [(18)F]-FB-anti-MMR 3.49 sdAb was synthesized with a 5-10% radiochemical yield using an automated and optimized protocol. In vivo biodistribution analyses showed retention in MMR-expressing organs, including tumor, and clearance via the kidneys. The kidney retention of the fluorinated sdAb was 20-fold lower compared to a (99m)Tc-labeled counterpart. Compared to MMR- and C-C chemokine receptor 2 (CCR2)-deficient mice, significantly higher uptake was observed in tumors grown in WT mice demonstrating the specificity of the (18)F-tracer for MMR and macrophages, respectively. Anti-MMR 3.49 was denoted as the lead cross-reactive MMR-targeting sdAb. [(18)F]-radiosynthesis was optimized, providing an optimal probe for PET imaging of the tumor-promoting macrophage subpopulation in the tumor stroma. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 06/2015; DOI:10.2967/jnumed.115.156828 · 5.56 Impact Factor
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    ABSTRACT: Monocytes consist of two well-defined subsets, the Ly6C+ and Ly6C- monocytes. Both CD11b+ myeloid cells populations have been proposed to infiltrate tissues during inflammation. While infiltration of Ly6C+ monocytes is an established pathogenic factor during hepatic inflammation, the role of Ly6C- monocytes remains elusive. Mice suffering experimental African trypanosome infection die from systemic inflammatory response syndrome (SIRS) that is initiated by phagocytosis of parasites by liver myeloid cells and culminates in apoptosis/necrosis of liver myeloid and parenchymal cells that reduces host survival. C57BL/6 mice are considered as trypanotolerant to Trypanosoma congolense infection. We have reported that in these animals, IL-10, produced among others by myeloid cells, limits the liver damage caused by pathogenic TNF-producing Ly6C+ monocytes, ensuring prolonged survival. Here, the heterogeneity and dynamics of liver myeloid cells in T. congolense-infected C57/BL6 mice was further dissected. Moreover, the contribution of Ly6C- monocytes to trypanotolerance was investigated. By using FACS analysis and adoptive transfer experiments, we found that the accumulation of Ly6C- monocytes and macrophages in the liver of infected mice coincided with a drop in the pool of Ly6C+ monocytes. Pathogenic TNF mainly originated from Ly6C+ monocytes while Ly6C- monocytes and macrophages were major and equipotent sources of IL-10 within myeloid cells. Moreover, Nr4a1 (Nur77) transcription factor-dependent Ly6C- monocytes exhibited IL-10-dependent and cell contact-dependent regulatory properties contributing to trypanotolerance by suppressing the production of TNF by Ly6C+ monocytes and by promoting the differentiation of the latter cells into macrophages. Thus, Ly6C- monocytes can dampen liver damage caused by an extensive Ly6C+ monocyte-associated inflammatory immune response in T. congolense trypanotolerant animals. In a more general context, Ly6C- or Ly6C+ monocyte targeting may represent a therapeutic approach in liver pathogenicity induced by chronic infection.
    PLoS Pathogens 05/2015; 11(5):e1004873. DOI:10.1371/journal.ppat.1004873 · 8.06 Impact Factor
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    ABSTRACT: Author Summary Extracellular trypanosomes, causative agents of sleeping sickness and Nagana, threaten human and animal health throughout the world. Anemia is a hallmark feature of virtually every type of trypanosome infection. During the early phase of experimental murine trypanosomosis, acute anemia occurs as witnessed by a 50% reduction in red blood cells within a 48 hour time span. The acute nature of this phenomenon suggests the implication of a consumptive process such as erythrophagocytosis. However, due to the multiple significant drawbacks of the presently used phagocytosis techniques, this has never been straightforwardly demonstrated. Here we developed a new erythrophagocytosis assay based on the labeling of red blood cells with the acid-sensitive dye pHrodo. This assay unequivocally distinguishes erythrophagocytozing cells in vivo and in vitro via flow cytometry and fluorescent microscopy. Using this new assay, we show that the acute anemia during experimental trypanosomosis is a result of enhanced erythrophagocytosis by activated liver monocytic cells and neutrophils as well as by activated splenic macrophages. Moreover, the red blood cell membrane composition and stability are altered during the infection, priming them for enhanced clearance by the myeloid phagocytic system.
    PLoS neglected tropical diseases 03/2015; 9(2):e0003561. DOI:10.1371/journal.pntd.0003561 · 4.72 Impact Factor
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    ABSTRACT: Pancreas injury by partial duct ligation (PDL) activates a healing response, encompassing β-cell neogenesis and proliferation. Macrophages were recently shown to promote β-cell proliferation after PDL, but they remain poorly characterized. We assessed myeloid cell diversity and the factors driving myeloid cell dynamics following acute pancreas injury by PDL. In naive and sham-operated pancreas, the myeloid cell compartment consisted mainly of two distinct tissue-resident macrophage types, designated MHC-IIlo and MHC-IIhi macrophages, the latter being predominant. MHC-IIlo and MHC-IIhi pancreas macrophages differed at the molecular level, with MHC-IIlo macrophages being more M2-activated. After PDL, there was an early surge of Ly6Chi monocyte infiltration in the pancreas, followed by a transient MHC-IIlo macrophage peak and ultimately a restoration of the MHC-IIhi macrophage-dominated steady-state equilibrium. These intricate macrophage dynamics in PDL pancreas depended on monocyte recruitment by CCR2 and M-CSFR as well as on M-CSFR-dependent local macrophage proliferation. Functionally, MHC-IIlo macrophages were more angiogenic. We further demonstrated that, at least in CCR2-KO mice, tissue macrophages, rather than Ly6Chi monocyte-derived macrophages, contributed to β-cell proliferation. Together, our study fully characterizes the macrophage subsets in the pancreas and clarifies the complex dynamics of macrophages after PDL injury.This article is protected by copyright. All rights reserved
    European Journal of Immunology 01/2015; 45(5). DOI:10.1002/eji.201445013 · 4.52 Impact Factor
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    ABSTRACT: African trypanosomosis is a chronic debilitating disease affecting the health and economic well-being of developing countries. The immune response during African trypanosome infection consisting of a strong proinflammatory M1-type activation of the myeloid phagocyte system (MYPS) results in iron deprivation for these extracellular parasites. Yet, the persistence of M1-type MYPS activation causes the development of anemia (anemia of chronic disease, ACD) as a most prominent pathological parameter in the mammalian host, due to enhanced erythrophagocytosis and retention of iron within the MYPS thereby depriving iron for erythropoiesis. In this review we give an overview of how parasites acquire iron from the host and how iron modulation of the host MYPS affects trypanosomosis-associated anemia development. Finally, we also discuss different strategies at the level of both the host and the parasite that can/might be used to modulate iron availability during African trypanosome infections.
    01/2015; 2015:1-15. DOI:10.1155/2015/819389
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    ABSTRACT: The current review article describes the functional relationship between tumor-associated macrophages (TAM) as key cellular contributors to cancer malignancy on the one hand and macrophage-colony-stimulating factor (M-CSF or CSF-1) as an important molecular contributor on the other. We recapitulate the available data on expression of M-CSF and the M-CSF receptor (M-CSFR) in human tumor tissue as constituents of a stromal macrophage signature and on the limits of the predictive and prognostic value of plasma M-CSF levels. After providing an update on current insights into the nature of TAM heterogeneity at the level of M1/M2 phenotype and TAM subsets, we give an overview of experimental evidence, based on genetic, antibody-mediated, and pharmacological disruption of M-CSF/M-CSFR signaling, for the extent to which M-CSFR signaling can not only determine the TAM quantity, but can also contribute to shaping the phenotype and heterogeneity of TAM and other related tumor-infiltrating myeloid cells (TIM). Finally, we review the accumulating information on the - sometimes conflicting - effects blocking M-CSFR signaling may have on various aspects of cancer progression such as tumor growth, invasion, angiogenesis, metastasis, and resistance to therapy and we thereby discuss in how far these different effects actually reflect a contribution of TAM.
    Frontiers in Immunology 10/2014; 5:489. DOI:10.3389/fimmu.2014.00489
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    ABSTRACT: Kupffer cells (KCs) are liver resident macrophages which are important for tissue homeostasis and have been implicated in immunogenic, tolerogenic and pathogenic immune reactions depending on the insult. These cells and the biomarkers they express thus represent interesting in vivo sensors for monitoring liver inflammation. In the current study, we explored whether KCs can be monitored non-invasively using single-photon-emission computed tomography (SPECT) with 99mTc labeled nanobodies (Nbs) targeting selected biomarkers. Nbs targeting V-set and immunoglobulin domain-containing 4 (Vsig4) or macrophage mannose receptor (MMR) accumulated in the liver of untreated mice. The liver targeting of anti-Vsig4 Nbs, but not anti-MMR Nbs, was blunted upon depletion of macrophages, highlighting specificity of anti-Vsig4 Nbs for liver macrophage imaging. Ex vivo flow cytometry and immunohistochemistry analysis confirmed that anti-Vsig4 Nbs specifically targeted KCs but no other cell types in the liver. Upon induction of acute hepatitis using concanavalin A (ConA), down-regulation of the in vivo imaging signal obtained using anti-Vsig4 Nbs reflected reduction in KC numbers and transient modulation of Vsig4 expression on KCs. Overall, these results indicate that Nbs targeting Vsig4 as molecular imaging biomarker enable non-invasive monitoring of KCs during hepatic inflammation.
    Immunobiology 10/2014; 220(2). DOI:10.1016/j.imbio.2014.09.018 · 3.18 Impact Factor
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    ABSTRACT: The life cycle of African trypanosomes involves adaptations to the defense mechanisms of two completely different hosts, the insect vector Glossina and the mammalian host. This interplay ultimately determines host resistance and/or tolerance to parasite infection. In the tsetse fly, the immune deficiency (IMD)-regulated pathway, the scavenger receptor peptidoglycan-recognition protein LB (PGRP-LB), and the reactive oxygen species (ROS)-mediated response modulate the insect's capacity to transmit the parasite. In experimental mice, control of parasite burden and tissue pathogenicity relies on timely regulated interactions between myeloid cells exhibiting distinct activation states (M1 versus M2 type). Tsetse fly saliva and various trypanosome components including adenylate cyclases, DNA, a kinesin heavy chain, and variant surface glycoprotein (VSG) interfere with resistance and tolerance to infection.
    Trends in Parasitology 09/2014; DOI:10.1016/ · 6.22 Impact Factor
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    ABSTRACT: 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 Ly6Chigh 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.
    PLoS Pathogens 09/2014; 10(9):e1004414. DOI:10.1371/journal.ppat.1004414 · 8.14 Impact Factor
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    PLoS Neglected Tropical Diseases 09/2014; 8(9):e3132. DOI:10.1371/journal.pntd.0003132 · 4.49 Impact Factor
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    ABSTRACT: An accurate and noninvasive tracer able to detect molecular events underlying the development of rheumatoid arthritis (RA) would be useful for RA diagnosis and drug efficacy assessment. A complement receptor of the Ig superfamily (CRIg) is expressed on synovial macrophages of RA patients, making it an interesting target for molecular imaging of RA. We aim to develop a radiotracer for the visualization of CRIg in a mouse model for RA using radiolabeled single-domain variable antibody VHH fragments (Nanobodies). Quantitative polymerase chain reaction was used to locate CRIg expression in mice with collagen-induced arthritis (CIA). A Nanobody, NbV4m119, was generated to specifically target CRIg. Flow cytometry, phosphorimaging, and confocal microscopy were used to confirm NbVm119 binding to CRIg-positive cells. SPECT (SPECT/CT) was used to image arthritic lesions in the inflamed paws of 29 mice using (99m)Tc-NbV4m119 Nanobody. CRIg is constitutively expressed in the liver and was found to be upregulated in synovial tissues of CIA mice. SPECT/CT imaging revealed that (99m)Tc-NbV4m119 specifically targeted CRIg-positive liver macrophages in naïve wild-type but not in CRIg(-/-) (CRIg knockout) mice. In CIA mice, (99m)Tc-NbV4m119 accumulation in arthritic lesions increased according to the severity of the inflammation. In the knees of mice with CIA, (99m)Tc-NbV4m119 was found to accumulate even before the onset of macroscopic clinical symptoms. SPECT/CT imaging with (99m)Tc-NbV4m119 visualizes joint inflammation in CIA. Furthermore, imaging could predict which mice will develop clinical symptoms during CIA. Consequently, imaging of joint inflammation with CRIg-specific Nanobodies offers perspectives for clinical applications in RA patients.
    Journal of Nuclear Medicine 03/2014; 55(5). DOI:10.2967/jnumed.113.130617 · 5.56 Impact Factor
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    ABSTRACT: To increase the safety and possibly efficacy of HIV-1 derived lentivectors (LVs) as an anti-cancer vaccine, we recently developed the Nanobody (Nb) display technology to target LVs to antigen presenting cells (APCs). In this study, we extend these data with exclusive targeting of LVs to conventional dendritic cells (DCs), which are believed to be the main cross-presenting APCs for the induction of a TH1-conducted antitumor immune response. The immunogenicity of these DC-subtype targeted LVs was compared to that of broad tropism, general APC-targeted and non-infectious LVs. Intranodal immunization with ovalbumin encoding LVs induced proliferation of antigen specific CD4+ T cells, irrespective of the LVs' targeting ability. However, the cytokine secretion profile of the restimulated CD4+ T cells demonstrated that general APC targeting induced a similar TH1-profile as the broad tropism LVs while transduction of conventional DCs alone induced a similar and less potent TH1 profile as the non-infectious LVs. This observation contradicts the hypothesis that conventional DCs are the most important APCs and suggests that the activation of other APCs is also meaningful. Despite these differences, all targeted LVs were able to stimulate cytotoxic T lymphocytes, be it to a lesser extent than broad tropism LVs. Furthermore this induction was shown to be dependent on type I interferon for the targeted and non-infectious LVs, but not for broad tropism LVs. Finally we demonstrated that the APC-targeted LVs were as potent in therapy as broad tropism LVs and as such deliver on their promise as safer and efficacious LV-based vaccines.
    Oncotarget 01/2014; 5(3). · 6.63 Impact Factor
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    ABSTRACT: Background Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication of combined antiretroviral therapy (cART) in HIV-TB co-infected patients. However, the disease mechanism is poorly understood, prognosis of TB-IRIS is currently impossible, and diagnosis is highly challenging. We analyzed whether the gene expression of monocytes could be correlated with TB-IRIS pathogenesis and could be used to classify patients predisposed to TB-IRIS. Methods Monocyte gene expression was compared between patients who developed TB-IRIS and matched controls. We carried out whole-genome expression profiling using Affymetrix GeneChip® ST 1.1 arrays at two time-points: before cART initiation (baseline) and at week two post-cART initiation. For each time-point, we used different statistical approaches to identify molecular signatures which could be used as classifiers. We also functionally mapped the modulated cellular pathways using the software package Ingenuity Pathway Analysis. Results At baseline, before introduction of cART and before onset of symptoms, monocyte gene expression was already perturbed in patients who subsequently developed TB-IRIS, indicating a possible involvement of monocytes in TB-IRIS predisposition. The differences in monocyte gene expression in TB-IRIS patients became even more clear after two weeks of cART (when TB-IRIS commonly occurs), with more than 100 genes for which expression showed a fold change greater than 1.5. Both at baseline and at week two post-cART initiation, a classifier of 8 and 9 genes, respectively could be built, which allowed discrimination of TB-IRIS cases and controls. Pathway analyses revealed that the majority of the dysregulated genes in TB-IRIS – at the time of the IRIS episode, but also already at baseline – are associated with infection and inflammation. Relevant biological functions which were perturbed before/during TB-IRIS included “Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses” and “Complement System”. Conclusion Our results indicate an involvement of monocytes in predisposition to/development of TB-IRIS, and suggest a number of functional pathways which may play a role in TB-IRIS development. This comprehensive study of gene regulation in monocytes provides baseline data for further studies into biomarkers for prognosis and diagnosis of TB-IRIS.
    Immunobiology 01/2014; 219(1):37–44. DOI:10.1016/j.imbio.2013.07.004 · 3.18 Impact Factor
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    ABSTRACT: Tumor-associated macrophages (TAM) are exposed to multiple microenvironmental cues in tumors, which collaborate to endow these cells with protumoral activities. Hypoxia, caused by an imbalance in oxygen supply and demand due to a poorly organized vasculature, is often a prominent feature in solid tumors. However, to what extent tumor hypoxia regulates the TAM phenotype in vivo is unknown. Here, we show that the myeloid infiltrate in mouse lung carcinoma tumors encompasses two morphologically distinct CD11bhiF4/80hiLy6Clo TAM subsets, designated as MHC-II(lo) and MHC-II(hi) TAM, both of which were derived from tumor-infiltrating Ly6C(hi) monocytes. MHC-II(lo) TAM express higher levels of prototypical M2 markers and reside in more hypoxic regions. Consequently, MHC-II(lo) TAM contain higher mRNA levels for hypoxia-regulated genes than their MHC-II(hi) counterparts. To assess the in vivo role of hypoxia on these TAM features, cancer cells were inoculated in PHD2-haplodeficient mice, resulting in better oxygenated tumors. Interestingly, reduced tumor hypoxia did not alter the relative abundance of TAM subsets nor their M2 marker expression, but specifically lowers hypoxia-sensitive gene expression and angiogenic activity in the MHC-II(lo) TAM subset. The same observation in PHD2(+/+) → PHD2(+/-) bone marrow chimeras also suggests organization of a better-oxygenized microenvironment. Together, our results show that hypoxia is not a major driver of TAM subset differentiation, but rather specifically fine-tunes the phenotype of M2-like MHC-II(lo) TAM.
    Cancer Research 11/2013; 74(1). DOI:10.1158/0008-5472.CAN-13-1196 · 9.28 Impact Factor
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    ABSTRACT: Tumor growth coincides with an accumulation of myeloid-derived suppressor cells (MDSCs) which exert immune suppression and which consist of two main subpopulations, known as monocytic CD11b(+) CD115(+) Ly6G(-) Ly6C(high) MO-MDSCs and granulocytic CD11b(+) CD115(-) Ly6G(+) Ly6C(int) PMN-MDSCs. However, whether these distinct MDSC subsets hamper all aspects of early CD8(+) T-cell activation - including cytokine production, surface marker expression, survival and cytotoxicity - is currently unclear. Here, employing an in vitro co-culture system, we demonstrate that splenic MDSC subsets suppress antigen-driven CD8(+) T-cell proliferation, but differ in their dependency on IFN-γ, STAT-1, IRF-1 and NO to do so. Moreover, MO- and PMN-MDSCs diminish IL-2 levels, but only MO-MDSCs affect IL-2Rα (CD25) expression and STAT-5 signaling. Unexpectedly however, both MDSC populations stimulate IFN-γ production by CD8(+) T cells on a per-cell basis, illustrating that some T-cell activation characteristics are actually stimulated by MDSCs. Conversely, MO-MDSCs counteract the activation-induced change in CD44, CD62L, CD162 and granzyme B expression, while promoting CD69 and Fas upregulation. Together, these effects result in an altered CD8(+) T-cell adhesiveness to the extracellular matrix and selectins, sensitivity to FasL-mediated apoptosis and cytotoxicity. Hence, MDSCs intricately influence different CD8(+) T-cell activation events in vitro, whereby some parameters are suppressed while others are stimulated. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 11/2013; 43(11). DOI:10.1002/eji.201343349 · 4.52 Impact Factor
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    ABSTRACT: In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells. By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO) synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time. A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity.
    PLoS Pathogens 10/2013; 9(10):e1003731. DOI:10.1371/journal.ppat.1003731 · 8.06 Impact Factor
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    Dataset: 2198b
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    ABSTRACT: 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).
    15th International Congress of Immunology (ICI) 22 Aug - 27 Aug, 2013., Milan, Italy; 08/2013
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Publication Stats

10k Citations
1,555.61 Total Impact Points


  • 1977–2015
    • Vrije Universiteit Brussel
      • • Laboratory of Cellular and Molecular Immunology
      • • Cellular Immunology (CMIM)
      • • Institute of Molecular Biology
      Bruxelles, Brussels Capital, Belgium
  • 1996–2010
    • Vlaams Instituut voor Biotechnologie
      • Laboratory for Molecular Cancer Biology
      Gand, Flemish, Belgium
  • 2009
    • University of Zambia
      • Department of Paraclinical Studies
      Lusaka, Lusaka Province, Zambia
  • 2004
    • The Police Academy of the Czech Republic in Prague
      Praha, Praha, Czech Republic
  • 1993–2003
    • Université Libre de Bruxelles
      • • Institute of Molecular Biology and Medicine (IBMM)
      • • Department of Molecular Biology
      Bruxelles, Brussels Capital Region, Belgium
  • 2002
    • University of Zurich
      • Internal Medicine Unit
      Zürich, ZH, Switzerland
  • 1995–2002
    • University of Liège
      • Laboratory of Tissue Biology
      Luik, Walloon, Belgium
  • 1993–2001
    • Molecular and Cellular Biology Program
      • Institute of Molecular Biology and Biotechnology
      Seattle, Washington, United States
  • 1994–1999
    • University Hospital Brussels
      Bruxelles, Brussels Capital, Belgium
    • KU Leuven
      • Department of Microbiology and Immunology
      Leuven, VLG, Belgium
  • 1992
    • Ghent University
      • Faculty of Veterinary Medicine
      Gent, VLG, Belgium
  • 1991
    • Institut Pasteur de Lille
      Lille, Nord-Pas-de-Calais, France
  • 1983
    • Ben-Gurion University of the Negev
      • Faculty of Health Sciences
      Beersheba, Southern District, Israel
  • 1981–1983
    • Weizmann Institute of Science
      • Department of Immunology