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Geanncarlo Lugo-Villarino

Summary

Molecular and cellular immunologist with an emphasis in host-pathogen interactions
ORCID: http://orcid.org/0000-0003-4620-8491

Projects

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Lucie Bernard, G. Lugo-Villarino & Pauline Schmitt

Mycobacterium tuberculosis and the host microbiome

In October 2015, thanks to the support of a Young Investigator award from the French National Research Agency (ANR), I was able to recruit Lucie Bernard as a PhD candidate to work on the MMI-TB research program. Our research focused on the use of commensal bacteria strains from pulmonary origin to modulate immunity against Mycobacterium tuberculosis. This approach involved the screening of bacterial strains (from a lung microbiota collection from the Philippe Langella laboratory) delivered intranasally to naïve mice, which were able to modulate the T cell populations in the lung. As such, we identified three pulmonary bacterial strains with the capacity to induce an anti-inflammatory response characterized by an increase of regulatory T cells (Treg). One of these strains was able to decrease the over-inflammation generated during tuberculosis, accompanied by elevated levels of a particular Treg subset known as “biTregs”, without increasing the M. tuberculosis burden in the lungs. We are currently trying to decipher how these biTreg are generated and whether they are responsible for the decreased inflammation using different mouse model for gain-of-function and loss-of-function strategies. Of note, we have filed a patent (No. FR1903364) at the “French Institut national de la propriété industrielle (INPI)” to protect these novel findings. Lucie Bernard delivered oral and poster presentations of these results at the American Association of Immunologist (AAI) meeting held in San Diego (CA) in May 2019, and now she will defend her PhD thesis on January 13th, 2020.

 

How does Mycobacterium tuberculosis exacerbate HIV-1 infection?

In October 2016, thanks to the support of an “Axe Thématique Prioritaires” PhD scholarship from Paul Sabatier University, linked to our “without borders” laboratory (the LIA IM-TB/HIV #1167), we were able to recruit Maeva Dupont as a PhD candidate to work for the IM-TB/HIV research program. Together with Christel Vérollet (CRCN INSERM), we supervised this student for the past three years and we focused in the synergistic relationship between M. tuberculosis and HIV-1, which results in increased proliferation of both pathogens and associated pathogenesis, considerably worsening the prognosis for co-infected patients. Increased tuberculosis severity in such patients is largely a consequence of HIV-1-induced T-cell decay. By contrast, how Mtb exacerbates HIV-1-associated pathology in co-infected patients is still poorly understood. One possible link is through macrophages, which are both primary host cells for Mtb, and are an important cell population involved in HIV-1 pathogenesis. We recently demonstrated that macrophage-to-macrophage transmission of HIV-1 via tunneling nanotubes (TNTs), long-range membranous and F-actin-containing tubes, is increased in a Tuberculosis-associated microenvironment (Souriant et al. 2019 Cell Reports). For her PhD thesis, Maeva has now uncovered two molecular mechanisms involved in this phenomenon: 1) Siglec-1 (CD169) expression in TNT enhancing their stability and function, and 2) sub-optimal response to type-I interferon signaling to establish an antiviral activity. Maeva Dupont delivered oral and poster presentations of these results at Microbioccitanie held in Montpellier in February 2019, and now she will defend her PhD thesis in December 6th, 2019.

 

IMG_2548.jpgChristel Verollet, Maeva Dupont & G. Lugo-Villarino

Curriculum vitae

Background I received my PhD in immunology from Harvard University in 2006. My dissertation work in the Glimcher lab was funded by the National Science Foundation, and dealt with the characterization of transcription factors in murine dendritic cells. My keen interest in innate immunity led me to join the Traver lab at the University of California San Diego (UCSD), where I conducted pioneering work in the characterization of dendritic cells and eosinophils in zebrafish. This postdoctoral stage (2006-09) was sponsored by the National Institute of Health academic career development award. My curiosity drove me to perform a second postdoctoral stage (2009-13) in the Neyrolles lab at IPBS funded by an ATIP startin g grant and the “Fondation pour la Recherche Médicale”. In October 2013, I was recruited to CNRS as CRCN. As such, I investigate the role of multiple physiological (e.g. lung microbiota) and pathological (e.g. AIDS) contexts that influences the capacity of Mycobacterium tuberculosis to parasitize host cells, with a unique emphasis on macrophages. In October 2017, I received my HDR (Habilitation à Diriger de Recherches) diploma in Immunology from Paul Sabatier University.

Position CNRS/CRCN (since October 2013)

Grants 2015-2018 "Young Investigator" grant from Agence Nationale de la Recherche (ANR): ANR-15-CE15-0012          label ANR bleu CMJN.jpeg

Awards Travel Grant Scholarship, PHC Van Gogh, Campus France/Ministère de l'Europe des Affaires étrangèrs, France/Netherlands (2018 and 2019)

Patent No. FR1903364, entitled “Traitements des maladies respiratoires avec la bacterie Lactobacillus animalis

Inventor’s License “TRUC mice” Tbx21-/-.Rag2-/- (BALB/c) mice: Reference Harvard Case# HU6663

Scientific activity My scientific achievements consist of 33 original research articles and 14 literature reviews, accumulating 3000 citations with an h-index of 25, according to Google Scholar (Lugo-Villarino, Google Scholar).

Editorial activity Associate, Review and Topic Editor at Frontiers in Immunology.

Committee activity Member of the Scientific Committee at École Doctorale Biologie-Santé-Biotechnologies (N°151 Biologie/Santé), Toulouse

Mentoring activity (in Toulouse) 5 Doctorate, 5 Master, and 7 visiting/foreign students

Publications (Top Five since 2013)

(*Equal contribution; corresponding author)

  1. Souriant (…) Lugo-Villarino*, Vérollet*. (2019) Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages" Cell Rep
  2. Lugo-Villarino*, Troegeler* et al. (2018) The C-type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis. Front Immuno
  3. Lastrucci (...) Lugo-Villarino*, Cougoule*. (2015) Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16(+) monocyte population via the IL-10/STAT3 axis. Cell Re
  4. Troegeler (...) Neyrolles*, Lugo-Villarino*. (2014) An efficient siRNA-mediated gene silencing in primary human monocytes, dendritic cells and macrophages. Immunol Cell Bio
  5. Lefèvre*, Lugo-Villarino*, Meunier* et al. (2013) The C-type lectin receptors dectin-1, MR, and SIGNR3 contribute both positively and negatively to the macrophage response to Leishmania infantum. Immunity

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