Laboratory of Myeloid Cell Immunology

Brussels, Belgium

Laboratory of Myeloid Cell Immunology

Brussels, Belgium
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Chittezhath M.,Agency for Science, Technology and Research Singapore | Dhillon M.K.,Agency for Science, Technology and Research Singapore | Lim J.Y.,Agency for Science, Technology and Research Singapore | Laoui D.,Laboratory of Myeloid Cell Immunology | And 16 more authors.
Immunity | Year: 2014

Monocytes and macrophages are major components of the tumor microenvironment, but their contributions to human cancer are poorly understood. Weused molecular profiling combined with functional assays to investigate the role of these cells in human renal cell carcinoma (RCC). Blood monocytes fromRCC patients displayed a tumor-promoting transcriptional profile that supported functions like angiogenesis and invasion. Induction of this protumor phenotype required an interleukin-1 receptor (IL-1R)-dependent mechanism. Indeed, targeting of IL-1-IL-1R axis in a human RCC xenograft model abrogated the protumor phenotype of tumor-associated macrophages (TAMs) and reduced tumor growth invivo. Supporting this, meta-analysis of gene expression from human RCC tumors showed IL1B expression to correlate with myelomonocytic markers, protumor genes, and tumor staging. Analyzing RCC patient tumors confirmed the protumor phenotype of TAMs. These data provide direct evidence for a tumor-promoting role of monocytes and macrophages in human cancer and indicate IL-1-IL-1R as a possible therapeutic target. © 2014 Elsevier Inc.

Murray P.J.,St Jude Childrens Research Hospital | Allen J.E.,University of Edinburgh | Fisher E.A.,New York University | Gilroy D.W.,University College London | And 22 more authors.
Immunity | Year: 2014

Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments invitro and invivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only two types of activated macrophages, often termed M1 and M2. Here, we describe a set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation-with the goal of unifying experimental standards for diverse experimental scenarios. Collectively, we propose a common framework for macrophage-activation nomenclature. The description of macrophage activation status is contentious and confusing. Murray etal. propose a framework for macrophage-activation nomenclature. © 2014 Elsevier Inc.

Casazza A.,Vesalius Research Center | Laoui D.,Laboratory of Myeloid Cell Immunology | Laoui D.,Vrije Universiteit Brussel | Wenes M.,Vesalius Research Center | And 8 more authors.
Cancer Cell | Year: 2013

Recruitment of tumor-associated macrophages (TAMs) into avascular areas sustains tumor progression; however, the underlying guidance mechanisms are unknown. Here, we report that hypoxia-induced Semaphorin 3A (Sema3A) acts as an attractant for TAMs by triggering vascular endothelial growth factor receptor 1 phosphorylation through the associated holoreceptor, composed of Neuropilin-1 (Nrp1) and PlexinA1/PlexinA4. Importantly, whereas Nrp1 levels are downregulated in the hypoxic environment, Sema3A continues to regulate TAMs in an Nrp1-independent manner by eliciting PlexinA1/PlexinA4-mediated stop signals, which retain them inside the hypoxic niche. Consistently, gene deletion of Nrp1 in macrophages favors TAMs' entrapment in normoxic tumor regions, which abates their pro-angiogenic and immunosuppressive functions, hence inhibiting tumor growth and metastasis. This study shows that TAMs' heterogeneity depends on their localization, which is tightly controlled by Sema3A/Nrp1 signaling. © 2013 Elsevier Inc.

PubMed | Friedrich - Alexander - University, Erlangen - Nuremberg, Medical Biotechnology Center, Albert Ludwigs University of Freiburg and Laboratory of Myeloid Cell Immunology
Type: | Journal: Journal of virology | Year: 2017

The ectodomain of matrix protein 2 is a universal influenza A vaccine candidate that provides protection through antibody-dependent effector mechanisms. Here we compared the functional engagement of Fc Receptor family members by two M2e-specific monoclonal antibodies: mAb 37 (IgG1) and mAb 65 (IgG2a), which recognize a similar epitope in M2e with similar affinity. Binding of mAb 65 to influenza A virus-infected cells triggered all three activating mouse Fc receptors in vitro, whereas mAb 37 only activated FcRIII. Passive transfer of mAb 37 or mAb 65 in wild type, Fcer1gThere is increased awareness that protection by antibodies directed against viral antigens is also mediated by the Fc domain of these antibodies. These Fc-mediated effector functions are often missed in clinical assays, which are used for example to define correlates of protection induced by vaccines. The use of antibodies to prevent and treat infectious diseases is on the rise, and has proven a promising approach in our battle against newly emerging viral infections. It is now also realized that Fc receptors significantly enhance the in vivo protective effect of broadly neutralizing antibodies directed against the conserved parts of the influenza virus hemagglutinin. We show here that two M2e-specific monoclonal antibodies with close to identical antigen- binding specificity and affinity have a very different in vivo protective potential that is controlled by their capacity to interact with activating Fc receptors.

Caljon G.,Institute of Tropical Medicine | Caljon G.,Vrije Universiteit Brussel | Caljon G.,Laboratory of Myeloid Cell Immunology | Hussain S.,Vrije Universiteit Brussel | And 4 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

Tsetse flies are the main vectors of human and animal African trypanosomes. The Tsal proteins in tsetse fly saliva were previously identified as suitable biomarkers of bite exposure. A new competitive assay was conceived based on nanobody (Nb) technology to ameliorate the detection of anti-Tsal antibodies in mammalian hosts. A camelid-derived Nb library was generated against the Glossina morsitans morsitans sialome and exploited to select Tsal specific Nbs. One of the three identified Nb families (family III, TsalNb-05 and TsalNb-11) was found suitable for anti-Tsal antibody detection in a competitive ELISA format. The competitive ELISA was able to detect exposure to a broad range of tsetse species (G. morsitans morsitans, G. pallidipes, G. palpalis gambiensis and G. fuscipes) and did not cross-react with the other hematophagous insects (Stomoxys calcitrans and Tabanus yao). Using a collection of plasmas from tsetse-exposed pigs, the new test characteristics were compared with those of the previously described G. m. moristans and rTsal1 indirect ELISAs, revealing equally good specificities (> 95%) and positive predictive values (> 98%) but higher negative predictive values and hence increased sensitivity (> 95%) and accuracy (> 95%). We have developed a highly accurate Nb-based competitive immunoassay to detect specific anti-Tsal antibodies induced by various tsetse fly species in a range of hosts. We propose that this competitive assay provides a simple serological indicator of tsetse fly presence without the requirement of test adaptation to the vertebrate host species. In addition, the use of monoclonal Nbs for antibody detection is innovative and could be applied to other tsetse fly salivary biomarkers in order to achieve a multi-target immunoprofiling of hosts. In addition, this approach could be broadened to other pathogenic organisms for which accurate serological diagnosis remains a bottleneck. © 2015 Caljon et al.

De Vooght L.,Antwerp Institute of Tropical Medicine | Caljon G.,Antwerp Institute of Tropical Medicine | Caljon G.,Vrije Universiteit Brussel | Caljon G.,Laboratory of Myeloid Cell Immunology | And 6 more authors.
Microbial Cell Factories | Year: 2012

Background: Sodalis glossinidius, a gram-negative bacterial endosymbiont of the tsetse fly, has been proposed as a potential in vivo drug delivery vehicle to control trypanosome parasite development in the fly, an approach known as paratransgenesis. Despite this interest of S. glossinidius as a paratransgenic platform organism in tsetse flies, few potential effector molecules have been identified so far and to date none of these molecules have been successfully expressed in this bacterium.Results: In this study, S. glossinidius was transformed to express a single domain antibody, (Nanobody ®) Nb_An33, that efficiently targets conserved cryptic epitopes of the variant surface glycoprotein (VSG) of the parasite Trypanosoma brucei. Next, we analyzed the capability of two predicted secretion signals to direct the extracellular delivery of significant levels of active Nb_An33. We show that the pelB leader peptide was successful in directing the export of fully functional Nb_An33 to the periplasm of S. glossinidius resulting in significant levels of extracellular release. Finally, S. glossinidius expressing pelBNb_An33 exhibited no significant reduction in terms of fitness, determined by in vitro growth kinetics, compared to the wild-type strain.Conclusions: These data are the first demonstration of the expression and extracellular release of functional trypanosome-interfering Nanobodies ®in S. glossinidius. Furthermore, Sodalis strains that efficiently released the effector protein were not affected in their growth, suggesting that they may be competitive with endogenous microbiota in the midgut environment of the tsetse fly. Collectively, these data reinforce the notion for the potential of S. glossinidius to be developed into a paratransgenic platform organism. © 2012 De Vooght et al; BioMed Central Ltd.

Caljon G.,Institute of Tropical Medicine | Caljon G.,Vrije Universiteit Brussel | Caljon G.,Laboratory of Myeloid Cell Immunology | De Vooght L.,Institute of Tropical Medicine | Van Den Abbeele J.,Institute of Tropical Medicine
Journal of Invertebrate Pathology | Year: 2013

Blood feeding arthropods are responsible for the transmission of a large array of medically important infectious agents that include viruses, bacteria, protozoan parasites and helminths. The recent development of transgenic and paratransgenic technologies have enabled supplementing the immune system of these arthropod vectors with anti-pathogen effector molecules in view of compromising their vector competence for these microbial agents. The characteristics of the selected anti-pathogen compound will largely determine the efficacy and specificity of this approach. Low specificity will generally result in bystander effects, likely having a direct or indirect fitness cost for the arthropod. In contrast, the use of highly specific compounds from the adaptive immune system of vertebrates such as antibody derived fragments is more likely to enable highly specific effects without conferring a selective disadvantage to the (para)transgenic arthropods. Here, Nanobodies® are excellent candidates to increase the immune competence of arthropods. Moreover they were shown to exert a novel type of anti-pathogen activity that uniquely depends on their small size. © 2013 International Atomic Energy Agency.

Roelants K.,Vrije Universiteit Brussel | Fry B.G.,University of Queensland | Ye L.,Vrije Universiteit Brussel | Stijlemans B.,Vrije Universiteit Brussel | And 8 more authors.
PLoS Genetics | Year: 2013

The skin secretion of many amphibians contains an arsenal of bioactive molecules, including hormone-like peptides (HLPs) acting as defense toxins against predators, and antimicrobial peptides (AMPs) providing protection against infectious microorganisms. Several amphibian taxa seem to have independently acquired the genes to produce skin-secreted peptide arsenals, but it remains unknown how these originated from a non-defensive ancestral gene and evolved diverse defense functions against predators and pathogens. We conducted transcriptome, genome, peptidome and phylogenetic analyses to chart the full gene repertoire underlying the defense peptide arsenal of the frog Silurana tropicalis and reconstruct its evolutionary history. Our study uncovers a cluster of 13 transcriptionally active genes, together encoding up to 19 peptides, including diverse HLP homologues and AMPs. This gene cluster arose from a duplicated gastrointestinal hormone gene that attained a HLP-like defense function after major remodeling of its promoter region. Instead, new defense functions, including antimicrobial activity, arose by mutation of the precursor proteins, resulting in the proteolytic processing of secondary peptides alongside the original ones.Although gene duplication did not trigger functional innovation, it may have subsequently facilitated the convergent loss of the original function in multiple gene lineages (subfunctionalization), completing their transformation from HLP gene to AMP gene. The processing of multiple peptides from a single precursor entails a mechanism through which peptide-encoding genes may establish new functions without the need for gene duplication to avoid adaptive conflicts with older ones. © 2013 Roelants et al.

Schouppe E.,Laboratory of Myeloid Cell Immunology | Schouppe E.,Vrije Universiteit Brussel | Van Overmeire E.,Laboratory of Myeloid Cell Immunology | Van Overmeire E.,Vrije Universiteit Brussel | And 6 more authors.
Immunobiology | Year: 2013

Myeloid-derived suppressor cells are immature myeloid cells, consisting of a monocytic and a granulocytic fraction, that are known to suppress anti-tumor immune responses. Important targets of the immunosuppressive capacity of MDSC are CD8+ T cells, which are crucial cytotoxic effector cells in immunotherapeutic settings. CD8+ T-cell activation and differentiation comprises a well-orchestrated series of events, starting from early TCR-mediated signaling and leading to cytokine secretion, the expression of activation markers, proliferation and the differentiation into several subsets of effector and memory cells. In this review, we summarize the available data on how the production of reactive oxygen species, nitric oxide, the arginase-mediated depletion of l-arginine and Cystine depletion by MDSCs interfere with the signaling molecules necessary for normal CTL differentiation and activation. © 2013 Elsevier GmbH.

Goyvaerts C.,Vrije Universiteit Brussel | Kurt D.G.,Vrije Universiteit Brussel | Kurt D.G.,Laboratory of Myeloid Cell Immunology | Lint S.V.,Vrije Universiteit Brussel | And 9 more authors.
Oncotarget | Year: 2014

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.

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