Characterization of host-derived lipids altering the macrophage metabolism during TB and TB/HIV infections
Tuberculosis (TB) is the deadliest disease due to a single infectious agent (i.e. Mycobacterium tuberculosis). Its well-known synergy with the Human Immunodeficiency Virus (HIV-1), the etiological agent for AIDS, places an immense clinical and economic burden in resource-limited countries where co-infection with these pathogens is highly prevalent.
This PhD project linked to our “without borders” laboratory (LIA IM-TB/HIV) aims to demonstrate the role of host-derived eicosanoids generated during TB infection in modulating susceptibility of human macrophages to pathogens. Its central rationale is based on the fact that microbicidal (M1) macrophages conditioned with the eicosanoid-enriched fraction from pleural effusion (PE) of TB patients (PE-TB) switch their metabolic state from aerobic glycolysis to oxidative phosphorylation, lowering their capacity to control M. tuberculosis intracellular proliferation (Marín Franco et al. Cell Rep 2020). While PE-TB also fosters susceptibility against HIV-1 infection, it remains unknown whether its eicosanoid-enriched fraction is responsible for this exacerbation. We hypothesize that eicosanoids modulate intercellular communication processes, in particular tunneling nanotubes (TNT) formation and dynamics, which we showed to be involved in the cell-to-cell transfer of HIV-1 among macrophages (Dupont et al. eLife 2019).
Uncovering a role of pulmonary CD169+ macrophages in the context(s) of respiratory infection
CD169+ (Sialoadhesin, Siglec-1) macrophages form a specific subset of macrophages found in the spleen and lymph nodes. It was described to trap various antigens and deliver them to dendritic cells, which then engage in cross-presentation of exogenous antigens to activate CD8 T cells. According to the literature and preliminary data, CD169+ macrophages can be found in the alveolar macrophage compartment in the lung of healthy human and mice, and accumulate in Mtb-infected non-human primates (Dupont et al. eLife 2019) and mice. However, the role of these pulmonary leukocytes during TB and TB-associated co-infections remains unexplored. This PhD project aims at determining whether lung CD169+ macrophages play a role in the etiology of TB and TB-associated co-infections.
- In preparation: PhD in Immunology and Infectious diseases (2020- ), IPBS-Toulouse, under the supervision of Drs. Geanncarlo Lugo and Christel Vérollet - Funding: Ministry of Higher Education, Research and Innovation
- Diploma of the Ecole Normale Supérieure de Lyon (2019-2020)
- Master’s degree in virology, microbiology and immunology (2017-2019), Ecole Normale Supérieure de Lyon
- Bachelor’s degree in biology (2014-2017), Ecole Normale Supérieure de Lyon
- 2020 (6 months): Characterization of the anti-influenza properties of natural metabolites of the respiratory mucosa, Dr. Mustapha Si-Tahar’s laboratory, Research Center for Respiratory Pathologies (CEPR), Tours (France)
- 2019 (4 months): Study of the immune response in the context of Influenza/Staphylococcus aureus co-infection in a mouse model, Dr. Linda Wakim’s laboratory, Peter Doherty Institute, Melbourne (Australia)
- 2019 (8 months): Set up of an assay to detect neutralizing antibodies in HTLV-1c-positive patient sera, Dr. Damian Purcell’s laboratory, Peter Doherty Institute, Melbourne (Australia)
- 2018 (6 months): Identification of the role of NLRP3 inflammasome in Hepatitis C Virus infection, Dr. Eliane Meurs’ laboratory, Pasteur Institute, Paris (France)
- 2017 (2 months): In vitro effects of type-I interferons on HTLV-1a viral transmission, Dr. Renaud Mahieux’s laboratory, International Centre for Infectiology Research (CIRI), Lyon (France)
- 2016 (2 months): Analysis of the polymorph nuclear neutrophil activation in patients with myeloproliferative diseases, Dr. Chloé James’ laboratory, Biology of Cardiovascular Diseases, Bordeaux (France)
- Cezard, Monard, Guillon, Si-Tahar. Energy metabolism, an essential player in the fight against infection (2021) Med Sci (Paris) In press
- Daussy, Monard, (…) Hansen. The inflammasome components NLRP3 and ASC act in concert with IRGM to rearrange the Golgi during viral infections (2021) J Virol 95(3):e00826-20
- Ge, Monk, Monard, (…) Wakim. Neutrophils play an ongoing role in preventing bacterial pneumonia by blocking the dissemination of S. aureus from the upper to the lower airway (2020) Immunol Cell Biol 98(7):577-594
- Castagné, Guingand, Moderc, Monard. Bacterial genome editing using the CRISPR/Cas12a system (2018) Med Sci (Paris) 34(5):399-400