Arnaud MARCHANTMD, PhD
Arnaud is a senior research associate at the Fund for Scientific Research (F.R.S.-FNRS), Belgium. He is an MD, PhD and Clinical Pathologist of the Université Libre de Bruxelles. He acquired his post-doctoral research experience at the MRC Laboratories, The Gambia, and at the Weatherall Institute of Molecular Medicine, Oxford, UK. He has been a founding member and the chief scientific officer of the research centre ImmuneHealth. Arnaud teaches medical immunology at the Medical Faculty of the Université Libre de Bruxelles and is a teacher on international courses organized by the Pasteur Institute, the University of Sienna and the Université Pierre et Marie Curie. His research group is specialized in human immulogy and currently investigates two main research areas.
Ontogeny of the human immune systemUnderstanding the ontogeny of the human immune system is a prerequisite to developing efficient and safe interventions aimed at providing long-term protection against infectious pathogens or inflammatory disorders originating early in life. The immune system of the fœtus and the newborn infant had long been considered as ‘immature’. This insight is based on the observation that infectious diseases are often more severe or more prolonged in early life. However, fetal immune cells develop early during human gestation and can express effector and regulatory functions, indicating that the immune system is not fundamentally immature in early life, but differs from that of adults. In collaboration with clinicians at the Hôpital Erasme and Hôpital Saint-Pierre, Brussels, we have demonstrated that the human foetus is able to develop effector T cell responses to viral infections. However, our recent studies indicate that foetal effector T cell responses are limited by functional regulation. Ongoing research is aiming at dissecting the molecular mechanisms involved in this functional regulation. In collaboration with Dr David Vermijlen, Faculty of Pharmacy, ULB, we are studying the ontogeny of innate lymphocytes in the human foetus. These studies indicate that effector cells are programmed very early during human life.
Immunity to viral infections during pregnancyCytomegalovirus (CMV) is the most common cause of congenital infection and is transmitted to the foetus in about 30% of the cases of primary infection during pregnancy. Prevention of congenital infection is the most important target for the development of CMV vaccines. In collaboration with clinicians at the Hôpital Erasme, Brussels, we have demonstrated that primary infection during pregnancy is associated with the expansion of large frequencies of CMV-specific T and B lymphocytes. As observed during persistant viral infections, T and B lymphocytes are functionally regulated during primary CMV infection. Ongoing research is aiming at defining the molecular mechanisms involved in this functional regulation and its impact on viral control.
In collaboration with clinicians at the Hôpital Saint-Pierre, Brussels, we are studying the development of the immune system of HIV-exposed but uninfected (HEU) infants and their susceptibility to microbial infections. Epidemiological studies indicate that although they are not infected by HIV, HEU infants have a high susceptibility to infectious diseases and an increased risk of mortality. Although this high risk of severe infections probabaly involve multiple factors, evidence suggest that immune factors play an important role. Ongoing research is aiming at prospectively define the risk of severe infections in this population and at identifying immunological correlates of susceptibility.
Related publicationsHuygens A, S Lecomte, M Tackoen, V Olislagers, Y Demarcelle, W Burny, M Van Rysselberge, C Liesnard, M Larsen, V Appay, C Donner, A Marchant. Functional exhaustion limits effector CD4 and CD8 T cell responses to congenital CMV infection. 2015 Journal of Infectious Diseases pii: jiv071. [Epub ahead of print].
Dimova T, M Brouwer, F Gosselin, J Tassignon, O Leo, C Donner, A Marchant, D Vermijlen. Effector Vγ9Vδ2 T cells dominate the human fetal γδ T cell repertoire. 2015 Proceedings of the National Academy of Sciences pii: 201412058. [Epub ahead of print].
Huygens A, N Dauby, D Vermijlen, A Marchant. Immunity to cytomegalovirus in early life. 2014 Frontiers in Immunology. doi: 10.3389/fimmu.2014.00552 Dauby N, C Kummert, S Lecomte, C Liesnard, ML Delforge, C Donner and A Marchant. Primary human cytomegalovirus infection induces the expansion of virus-specific activated and atypical memory B cells. 2014 Journal of Infectious Diseases. 210:1275-1285.
Dauby N, T Goetghebuer, TR Kollmann, J Levy, A Marchant. Uninfected but not unaffected: chronic maternal infections during pregnancy, fetal immunity, and susceptibility to postnatal infections. 2012 The Lancet Infectious Diseases 12 :330-340. Antoine P, V Olislagers, A Huygens, S Lecomte, C Liesnard, C Donner, A Marchant. Functional exhaustion of CD4+ T lymphocytes during primary CMV infection. 2012 Journal of Immunology 189:2665-2672.
Epalza C, T Goetghebuer, M Hainaut, F Prayez, P Barlow, A Dediste, A Marchant, J Levy. High Incidence of Invasive Group B Streptococcal Infections in HIV-Exposed Uninfected Infants. 2010 Pediatrics 126:e631-638.
Vermijlen D, M Brouwer, C Donner, C Liesnard, M Tackoen, M Van Rysselberge, N Twité, M Goldman, A Marchant, F Willems. Human cytomegalovirus elicits fetal gamma delta T cell responses in utero. 2010 Journal of Experimental Medicine 207:807-821.
Marchant A, V Appay, M van der Sande, N Dulphy, C Liesnard, M Kidd, S Kaye, O Ojuola, GMA Gillespie, AL Vargas Cuero, V Cerundolo, M Callan, KPWJ McAdam, SL Rowland-Jones, C Donner, AJ McMichael, H Whittle. Mature CD8+ T lymphocyte response to viral infection during foetal life. 2003 Journal of Clinical Investigation 111:1747-1755.