Laboratory of Cellular and Molecular Immunology

Brussels, Belgium

Laboratory of Cellular and Molecular Immunology

Brussels, Belgium
SEARCH FILTERS
Time filter
Source Type

Nzoumbou-Boko R.,IRD Montpellier | Nzoumbou-Boko R.,University of Bordeaux 1 | De Muylder G.,Free University of Colombia | Semballa S.,IRD Montpellier | And 18 more authors.
Journal of Immunology | Year: 2017

Arginase activity induction in macrophages is an escape mechanism developed by parasites to cope with the host's immune defense and benefit from increased host-derived growth factor production. We report that arginase expression and activity were induced in macrophages during mouse infection by Trypanosoma musculi, a natural parasite of this host. This induction was reproduced in vitro by excreted/secreted factors of the parasite. A mAb directed to TbKHC1, an orphan kinesin H chain from Trypanosoma brucei, inhibited T. musculi excreted/secreted factor-mediated arginase induction. Anti-TbKHC1 Ab also inhibited T. musculi growth, both in vitro and in vivo. Induction of arginase activity and parasite growth involved C-type lectin receptors, because mannose injection decreased arginase activity induction and parasite load in vitro and in vivo. Accordingly, the parasite load was reduced in mice lacking mannose receptor C-type 1. The T. musculi KHC1 homolog showed high similarity with TbKHC1. Bioinformatics analysis revealed the presence of homologs of this gene in other trypanosomes, including pathogens for humans and animals. Host metabolism dysregulation represents an effective parasite mechanism to hamper the host immune response and modify host molecule production to favor parasite invasion and growth. Thus, this orphan kinesin plays an important role in promoting trypanosome infection, and its neutralization or the lock of its partner host molecules offers promising approaches to increasing resistance to infection and new developments in vaccination against trypanosomiasis. Copyright © 2017 by The American Association of Immunologists, Inc.


Muller G.C.,Laboratory of Cellular and Molecular Immunology | Pitrez P.M.,Grande Rio University | Teixeira A.L.,Federal University of Minas Gerais | Pires P.S.,Grande Rio University | And 3 more authors.
Clinical and Experimental Allergy | Year: 2010

Background Asthma is characterized by chronic inflammation of the airways with significant changes in leucocyte trafficking, cellular activation and tissue remodelling. Brain-derived neurotrophic factor (BDNF) has been involved with asthma and allergic diseases but its role as a severity marker in paediatric asthma has not been clinically assessed.Objectives To evaluate plasma BDNF and inflammatory markers in order to address their relationships with disease severity in children (6-15 years) with controlled persistent asthma.Methods Children with persistent asthma were selected and lung function and skin prick tests were performed in all patients. Plasma BDNF levels and various inflammatory markers (CCL3, CCL11, CCL22, CCL24, CXCL8, CXCL9, CXCL10, soluble TNF receptors) were assessed by ELISAs.Results Subjects with moderate and severe asthma had higher BDNF levels than mild asthma and controls (P<0.001). The chemokines studied and soluble TNF receptors did not differ between the studied groups.Conclusion and Clinical Relevance Our results indicate BDNF as a potential biomarker for clinical severity in children with asthma. © 2010 Blackwell Publishing Ltd.


Luyckx A.,Catholic University of Leuven | Schouppe E.,Laboratory of Cellular and Molecular Immunology | Schouppe E.,Vrije Universiteit Brussel | Rutgeerts O.,Catholic University of Leuven | And 9 more authors.
Bone Marrow Transplantation | Year: 2012

To date, myeloid-derived suppressor cells (MDSC) have been best studied in cancer, where they represent an escape mechanism for immune surveillance. MDSC are now also gaining interest in the context of transplantation. Suppressive CD11b myeloid progenitor cells have been reported to expand endogenously during BM chimerism induction in mice; in particular, in irradiated MHC-matched BM chimeras and in parent-in-F1 BM chimeras. Myeloid cell expansion coincided with a time frame where donor lymphocyte infusion (DLI) therapy-mediated GVL effects without GVHD. Hypothesizing that regulatory myeloid cells may have a role in regulating post-transplant T-cell alloreactivity, we performed a detailed phenotypic and functional characterization of these cells in the parent-in-F1 C57BL/6 C57BL/6xDBA2 model. We found that transiently expanding CD11b myeloid progenitor cells comprise the two phenotypically and functionally distinct mononuclear and polymorphonuclear MDSC subsets that were recently described in tumor-bearing mice. Both MDSC subsets suppressed in vitro and in vivo alloreactive T-cell proliferation. Also, both the subsets mediated enhanced in vitro suppression when harvested from chimeras, given a prior in vivo challenge with non-tolerant donor T cells, indicating that allo-activated T cells can activate MDSC in vivo. This study provides the basis to investigate thepotentially beneficialrole of expanding MDSC in influencing the risk of GVHD during chimerism induction. © 2012 Macmillan Publishers Limited.


Luyckx A.,Catholic University of Leuven | Schouppe E.,Laboratory of Cellular and Molecular Immunology | Schouppe E.,Vrije Universiteit Brussel | Rutgeerts O.,Catholic University of Leuven | And 8 more authors.
Clinical Immunology | Year: 2012

The role of myeloid-derived suppressor cells (MDSC) is emerging in transplantation. An expansion of myeloid progenitor cells with suppressive capacity has been reported to occur as a bystander phenomenon in the course of allogeneic hematopoietic stem cell transplantation (allo-HSCT) protocols, particularly, in mice during bone marrow chimerism induction and in human stem cell donors during G-CSF-mobilization protocols. Hypothesizing that such 'regulatory myeloid cells' play a role in regulating post-transplant T-cell alloreactivity, we performed a phenotypical and functional characterization of these cells in peripheral blood stem cell grafts of G-CSF-treated donors. We demonstrate that expanding myeloid cells in the peripheral blood of G-CSF-mobilized donors comprise the typical phenotype of the mononuclear and polymorphonuclear MDSC-subtypes that were recently described in cancer patients, and that both MDSC-subsets have the capacity to regulate alloreactive T-cell responses in-vitro. This study provides the basis for investigating the clinical relevance of MDSC and MDSC-subtypes in human allo-HSCT. © 2012 Elsevier Inc.


Nair S.S.,George Washington University | Bommana A.,George Washington University | Pakala S.B.,George Washington University | Ohshiro K.,George Washington University | And 10 more authors.
Hepatology | Year: 2011

Based on the recently established role for the master coregulator MTA1 and MTA1-containing nuclear remodeling complexes in oncogenesis and inflammation, we explored the links between parasitism by the carcinogenic liver fluke Opisthorchis viverrini and this coregulator using both an Mta1 -/- mouse model of infection and a tissue microarray of liver fluke-induced human cholangiocarcinomas (CCAs). Intense foci of inflammation and periductal fibrosis in the liver and kidneys of wild-type Mta1 +/+ mice were evident at 23 days postinfection with O. viverrini. In contrast, little inflammatory response was observed in the same organs of infected Mta1 -/- mice. Livers of infected Mta1 +/+ mice revealed strong up-regulation of fibrosis-associated markers such as cytokeratins 18 and 19 and annexin 2, as determined both by immunostaining and by reverse-transcription polymerase chain reaction compared with infected Mta1 -/- mice. CD4 expression was up-regulated by infection in the livers of both experimental groups; however, its levels were several-fold higher in the Mta1 +/+ mice than in infected Mta1 -/- mice. Mta1 -/- infected mice also exhibited significantly higher systemic and hepatic levels of host cytokines such as interleukin (IL)-12p70, IL-10, and interferon-γ compared with the levels of these cytokines in the Mta1 +/+ mice, suggesting an essential role of MTA1 in the cross-regulation of the Th1 and Th2 responses, presumably due to chromatin remodeling of the target chromatin genes. Immunohistochemical analysis of ≈300 liver tissue cores from confirmed cases of O. viverrini-induced CCA showed that MTA1 expression was elevated in >80% of the specimens. Conclusion: These findings suggest that MTA1 status plays an important role in conferring an optimal cytokine response in mice following infection with O. viverrini and is a major player in parasite-induced CCA in humans. © 2011 American Association for the Study of Liver Diseases.


Van Ginderachter J.A.,Laboratory of Cellular and Molecular Immunology | Van Ginderachter J.A.,Vrije Universiteit Brussel | Beschin A.,Laboratory of Cellular and Molecular Immunology | Beschin A.,Vrije Universiteit Brussel | And 4 more authors.
European Journal of Immunology | Year: 2010

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immatureb myeloid cells that share a common property of suppressing immune responses. Several helminth and protozoan parasite species have developed efficient strategies to increase the rate of medullary or extramedullary myelopoiesis and to induce the expansion and accumulation of immature myeloid cells such as MDSC. In this review, we examine current knowledge on the factors mediating enhanced myelopoiesis and MDSC induction and recruitment during parasitic infections and how the MDSC phenotype and mechanism of immune modulation and suppression depends on the factors they encounter within the host. Finally, we place MDSC expansion in the context of the critical balance between parasite elimination and pathogenicity to the host and suggest attractive avenues for future research. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Buelens K.,Catholic University of Leuven | Hassanzadeh-Ghassabeh G.,Laboratory of Cellular and Molecular Immunology | Hassanzadeh-Ghassabeh G.,Vrije Universiteit Brussel | Muyldermans S.,Laboratory of Cellular and Molecular Immunology | And 3 more authors.
Journal of Thrombosis and Haemostasis | Year: 2010

Background and objective: As activated thrombin-activatable fibrinolysis inhibitor (TAFIa) is a potent antifibrinolytic enzyme, the development of TAFI inhibitors is a new promising approach in the development of profibrinolytic drugs. We, therefore, aimed to generate nanobodies, camelid-derived single-domain antibodies towards TAFI. Methods and results: This study reports the generation and characterization of a panel of 22 inhibitory nanobodies. This panel represents a wide diversity in mechanisms for interference with the functional properties of TAFI as the nanobodies interfere with various modes of TAFI activation, TAFIa activity and/or TAFI zymogen activity. Nanobodies inhibiting TAFIa activity and thrombin/thrombomodulin-mediated TAFI activation revealed profibrinolytic properties in a clot lysis experiment with exogenously added thrombomodulin (TM), whereas nanobodies inhibiting plasmin-mediated TAFI activation only revealed profibrinolytic properties in a clot lysis experiment without TM. The results of in vitro clot lysis experiments provided evidence that inhibitory nanobodies penetrate the clot better compared with inhibitory monoclonal antibodies. Conclusions: These data suggest that the generated nanobodies are potent TAFI inhibitors and are a step forward in the development of a profibrinolytic drug. They might also be an excellent tool to unravel the role of the physiological activators of TAFI in various pathophysiological processes. © 2010 International Society on Thrombosis and Haemostasis.


Batista S.A.,Federal University of Minas Gerais | Rocha G.A.,Federal University of Minas Gerais | Rocha A.M.C.,Federal University of Minas Gerais | Saraiva I.E.B.,Federal University of Minas Gerais | And 3 more authors.
BMC Microbiology | Year: 2011

Background: Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between H. pylori CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis. Results: The number of EPIYA C segments was significantly associated with the increased risk of gastric carcinoma (OR = 3.08, 95% CI = 1.74 to 5.45, p < 10-3) even after adjustment for age and gender. Higher number of EPIYA C segments was also associated with gastric atrophy (p = 0.04) and intestinal metaplasia (p = 0.007). Furthermore, patients infected by cagA strains possessing more than one EPIYA C segment showed decreased serum levels of pepsinogen I in comparison with those infected by strains containing one or less EPIYA C repeat. Otherwise, the number of EPIYA C segments did not associate with duodenal ulcer. Conclusions: Our results demonstrate that infection with H. pylori strains harbouring more than one CagA EPIYA C motif was clearly associated with gastric cancer, but not with duodenal ulcer. Higher number of EPIYA C segments was also associated with gastric precancerous lesions as demonstrated by histological gastric atrophic and metaplastic changes and decreased serum levels of pepsinogen I. © 2011 Batista et al; licensee BioMed Central Ltd.


Laoui D.,Vrije Universiteit Brussel | Laoui D.,Laboratory of Cellular and Molecular Immunology | Van Overmeire E.,Vrije Universiteit Brussel | Van Overmeire E.,Laboratory of Cellular and Molecular Immunology | And 16 more authors.
Immunobiology | Year: 2011

Mononuclear phagocytes are amongst the most versatile cells of the body, contributing to tissue genesis and homeostasis and safeguarding the balance between pro- and anti-inflammatory reactions. Accordingly, these cells are notoriously heterogeneous, functioning in distinct differentiation forms (monocytes, MDSC, macrophages, DC) and adopting different activation states in response to a changing microenvironment. Accumulating evidence exists that mononuclear phagocytes contribute to all phases of the cancer process. These cells orchestrate the inflammatory events during de novo carcinogenesis, participate in tumor immunosurveillance, and contribute to the progression of established tumors. At the tumor site, cells such as tumor-associated macrophages (TAM) are confronted with different tumor microenvironments, leading to TAM subsets with specialized functions. A better refinement of the molecular and functional heterogeneity of tumor-associated mononuclear phagocytes might pave the way for novel cancer therapies that directly target these tumor-supporting cells. © 2011 Elsevier GmbH.


PubMed | Laboratory of Cellular and Molecular Immunology
Type: Journal Article | Journal: European journal of immunology | Year: 2010

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that share a common property of suppressing immune responses. Several helminth and protozoan parasite species have developed efficient strategies to increase the rate of medullary or extramedullary myelopoiesis and to induce the expansion and accumulation of immature myeloid cells such as MDSC. In this review, we examine current knowledge on the factors mediating enhanced myelopoiesis and MDSC induction and recruitment during parasitic infections and how the MDSC phenotype and mechanism of immune modulation and suppression depends on the factors they encounter within the host. Finally, we place MDSC expansion in the context of the critical balance between parasite elimination and pathogenicity to the host and suggest attractive avenues for future research.

Loading Laboratory of Cellular and Molecular Immunology collaborators
Loading Laboratory of Cellular and Molecular Immunology collaborators