Ricardo Silvestre

  • Immunometabolism
  • inflammatory and infectious diseases
  • cell metabolism
  • immunity
  • macrophages
  • Leishmaniasis
  • drug discovery
  • vaccine

Ricardo Silvestre concluded in 2003 and 2007 his degree and PhD in Pharmaceutical Sciences at the Faculty of Pharmacy, University of Porto. His interest in Immunology and Parasitology led him in 2003 to the Institute Pasteur in Paris where, as an undergraduate student, participated in studies on the antigenic variation and nuclear architecture in the causative agent of human malaria, Plasmodium falciparum. During his PhD, he continued his studies in the field of Leishmania epigenetics, immune response and Leishmania vaccine development.
Between 2008-2010, he was a Postdoctoral research fellow at the Institut Mondor de Recherche Biomédicale, University of Paris-Est Créteil, France, addressing the role of mitochondrial dynamics in regulating programmed cell death during HIV infection and anti-HIV chemotherapy. From 2010 to 2014, he held an assistant researcher position at the Institute of Cell and Molecular Biology (IBMC), University of Porto, where he developed new approaches to understand the host immune mechanisms involved in the control/susceptibility to leishmaniasis.
Currently, he is PrincipaI Investigator at the Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho. His research interest is to integrate the study of basic molecular and cellular mechanisms to develop a greater understanding of the immune-metabolic interface occurring during an immune response. He addresses how the modifications of host cell metabolism and bioenergetics arising during inflammatory or infectious processes impact the immune functions of macrophage and dendritic cells and the further consequences to tissue homeostasis with the objective of developing new approaches to prevention and treatment.

Scientific Highlights

“André S, Picard M, Cezar R, Roux-Dalvai F, Alleaume-Butaux A, Soundaramourty C, Cruz AS, Mendes-Frias A, Gotti C, Leclercq M, Nicolas A, Tauzin A, Carvalho A, Capela C, Pedrosa J, Castro AG, Kundura L, Loubet P, Sotto A, Muller L, Lefrant JY, Roger C, Claret PG, Duvnjak S, Tran TA, Racine G, Zghidi-Abouzid O, Nioche P, Silvestre R, Droit A, Mammano F, Corbeau P, Estaquier J. T cell apoptosis characterizes severe Covid-19 disease. Cell Death and Differentiation. 2022 Jan 22:1-14
– Ferreira C, Estaquier J, Silvestre R.* Immune-metabolic interactions between Leishmania and macrophage host. Current Opinion in Microbiology 2021 63:231-237.
– Santa Cruz A, Mendes-Frias A, Oliveira AI, Dias L, Matos AR, Carvalho A, Capela C, Pedrosa J, Castro AG, Silvestre R. * IL-6 is a biomarker for the development of fatal SARS-CoV-2 pneumonia. Frontiers in Immunology 2021 12:613422
– Mesquita I, Ferreira C, Moreira D, Kluck GEG, Barbosa AM, Torrado E, Dinis-Oliveira RJ, Gonçalves LG, Beauparlant CJ, Droit A, Berod L, Sparwasser T, Bodhale N, Saha B, Rodrigues F, Cunha C, Carvalho A, Castro AG, Estaquier J, Silvestre R. * The Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis. Cell Reports 2020 Mar 24;30(12):4052-4064.e7
– Laforge M, Silvestre R, Rodrigues V, Garibal J, Campillo-Gimenez L, Mouhamad S, Monceaux V, Cumont MC, Rabezanahary H, Pruvost A, Cordeiro-da-Silva A, Hurtrel B, Silvestri G, Senik A, Estaquier J. The anticaspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques. Journal of Clinical Investigation 2018 128 (4): 1627-1640
– Arts RJW, Novakovic B, Horst R, Carvalho A, Bekkering S, Lachmandas E, Rodrigues F, Silvestre R, Cheng S, Wang S, Habibi E, Gonçalves LG, Mesquita I, Cunha C, Van Laarhoven A, Van de Veerdonk FL, Williams DL, Van der Meer JWM, Logie C, O’Neill LA, Dinarello CA, Riksen NP, Van Crevel R, Clish C, Notebaart RA, Joosten LAB, Stunnenberg HG, Xavier RJ, Netea MG. Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity Cell Metabolism 2016 13;24(6):807-819
– Moreira D, Rodrigues V, Abengozar M, Rivas L, Rial E, Laforge M, Li X, Foretz M, Viollet B, Estaquier J, Cordeiro da Silva A, Silvestre R. * Leishmania infantum Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis. PLoS Pathogens 2015 Mar 4;11(3):e1004684
– Rodrigues V, Laforge M, Campillo-Gimenez L, Soundaramourty C, Correia-de-Oliveira A, Dinis-Oliveira RJ, Ouaissi A, Cordeiro-da-Silva A, Silvestre R* and Estaquier J.* Abortive T follicular helper development is associated with a defective humoral response in Leishmania infantum-infected macaques. PLoS Pathogens 2014 10(4):e1004096.
– Silvestre R., Cordeiro-da-Silva A., Santarém N., Vergnes B., Sereno D. and Ouaissi A. SIR2-deficient Leishmania infantum induces a defined IFN-gamma/IL-10 pattern that correlates with protection. Journal of Immunology. 2007, 179 (5); 3161-3170.
– Freitas-Junior LH, Hernandez-Rivas R, Ralph SA, Montiel-Condado D, Ruvalcaba-Salazar OK, Rojas-Meza AP, Mancio-Silva L, Leal-Silvestre RJ, Gontijo AM, Shorte S and Scherf A. Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites. Cell. 2005, 121(1): 25-36.”


Gut microbiota, metabolites and host immunity

The intestinal epithelial barrier (EB) represents the largest interface between the internal organs and the environment. The precise regulation of the intestinal EB allows the maintenance of mucosal immune homeostasis and prevents the onset of uncontrolled inflammation.

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Host-fungus interaction and disease pathogenesis

The reprogramming of cellular metabolism is a fundamental mechanism whereby immune cells respond to infection. The sensing of microbial ligands by myeloid cells promotes dynamic changes in host cell metabolism to deliver a rapid source of energy to support…

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Immunometabolic networks on Leishmania infection

Innate immune cells tightly coordinate their metabolic programs to support a proper immunological function. As such, perturbed metabolic fluxes imply decisive effects on immune cell activation eventuating in their ability to control a pathogen and the disease inflicted by it.

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