Viral Infection & Chronicity

Bone marrow viral reservoirs and hematopoietic injury (FR)

We investigate whether HIV-1 (and selected RNA viruses) chronically infect hematopoietic stem and progenitor cells (HSPC) and megakaryocyte-biased progenitors, and whether terminally differentiated progeny inherit virus and dysfunction, thereby impairing immune homeostasis and immune reconstitution, in line with previous demonstrations by the team leader and group (J Mol Cell Biol 2024, Sci Trans Med 2020).  Using hiPSC-derived bone marrow organoids, primary human bone marrow and advanced megakaryocyte/platelet models, this axis will (i) map viral reservoirs in defined progenitor subsets, (ii) determine how infection remodels myelopoiesis (including non-canonical megakaryopoiesis and fibrosis), and (iii) evaluate how virus-containing megakaryocytes and platelets fuel peripheral immune injury and limit curative strategies such as HSPC transplantation.

Reprogramming of myeloid progenitors in Post-Acute Infection Syndromes (FR)

Building on trained immunity concepts and previous investigations by the team leader on immune-metabolic reprogramming on myeloid HIV reservoirs (Nat Commun 2022) we will first exploit clinically relevant trained immunity inducers to epigenetically educate HSPC and megakaryocyte progenitors toward an antiviral, low-inflammatory profile, aiming at durable reservoir restriction and improved immune restoration in people living with HIV.  In parallel, it will investigate how acute infection by SARS-CoV-2, IAV and emerging alphaviruses (MAYV/CHIKV, col. UFRJ-Brazil) imprints megakaryocyte progenitors to generate dysfunctional megakaryocytes that sustain viral persistence, tissue inflammation/fibrosis and hematopoietic aging in PAIS, and test interventions targeting these trained megakaryocytes in murine and human PAIS models.

Myeloid cell membranes as biocompatible platform for targeted antiviral therapies (FR)

Platelet membrane-cloaked nanoparticles are proposed as a biocompatible drug delivery platform to target and eliminate persistently HIV-infected cells.  By coating antiviral drug–loaded synthetic nanoparticles with platelet membranes, this biomimetic system improves specificity, reduces hemolysis, and enhances biodistribution.  Platelet membranes naturally home to inflammatory sites, interact with monocytes and CD4 T cells, and are cleared by tissue macrophages, enabling targeting of both lymphoid and myeloid HIV reservoirs in blood and tissues.  This versatile technology could be extended to other chronic viral infections (CIFRE, col. EFS, Centrale Lille).

Aging and respiratory infections (FT)

Despite the availability of various vaccines and antimicrobial drugs, aging worsens the outcomes of respiratory infections. Our general objective is to define age-associated factors that predispose to and/or exacerbate respiratory infections (acute and resolution phases). We aim to develop new strategies for reinforcing host’s defense against respiratory pathogens and/or to favoring repair processes that take place in the lungs. Within that framework, our team has a strong interest for the gut microbiota, which is known to be critical in human health and illness, including during respiratory infections. We expect that a better understanding of the gut/lung axis will be instrumental in conceiving novel therapeutic options for patients, notably in high-risk populations such as the elderly. We also have a strong interest in cellular senescence, a phenomenon that accelerates with aging and is a major contributor to so-called inflammaging.

Gut microbiota and aging (FT)

The gut microbiota plays a critical role in health and disease. Our group has recently patented several therapeutic applications in infections, including compounds produced by the gut microbiota such as short-chain fatty acids (ANR ACROBAT). We have shown that these metabolites attenuate secondary disease outcomes during influenza - including bacterial superinfection (Cell Reports 2020). More recently, we have characterized 3-indole propionic acid (IPA), a tryptophan microbial-derived metabolite, as an antiviral and anti-inflammatory component (Gut Microbes 2024, Start-AIRR IPA-VIR).  Pharmacological approaches, next-generation probiotics and postbiotics are being developed. These notably include bacterial strains selected for their strong anti-inflammatory potential and their ability to produce short-chain fatty acids or IPA in symbiosis with specific nutrients (Front Immunol 2024). We have reported the marked impact of influenza and SARS-CoV-2 on gut microbiota’s composition and function (Cell Reports 2020, Infect & Immun 2021, Gut Microbes 2020, 2022a, 2022b). This might be important in the long-term effect of respiratory viral infection.

Aging strongly influences the functionality of the gut microbiota. Our recent data demonstrate the importance of the age-related alteration of the gut microbiota in pulmonary defense against respiratory infection (ANR GUTSY). Moreover, the virus-induced dysbiosis is exacerbated in aged individuals and this likely plays a major part on disease severity (Gut Microbes 2025, Sci Report 2025). In collaboration with B. Lucas (Inst Cochin, Paris), we are investigating how an aged microbiota alters the T cell compartment and contributes to immune responses during influenza infection (MicrobioTaging, France 2030, PEPR SAM).

Cellular senescence and respiratory infections (FT)

We have a strong interest in cellular senescence, a biological process that affects cell function. We have recently investigated the role of age-associated, naturally occurring senescent cells, as well as stress- (virus-) induced senescent cells, during experimental influenza and COVID-19 (ANR INFLUENZAGING and SENOCOVID). To this end, we have developed complementary approaches, including pharmacological (senolytic) and genetic strategies (coll S Adnot, Inst Mondor). Our data show that respiratory infection associates with cellular senescence and that this phenomenon is exacerbated in old individuals (Am J Respir Cell Mol Biol 2022, Nature Aging 2023, Aging Cell 2025). Age-related cellular senescence favours the severity of COVID19 and influenza (Nature Aging 2023, Aging Cell 2025, submitted). In particular, senescent cells are important in mitigating the repair processes that occur in the lungs post-pneumonia. Our objective is to better characterize the nature of senescent cells during infection and to optimize protocol to more selectively deplete them (SENINFLU, submitted).

In addition to our focus on aging in the context of respiratory infection, our laboratory is also investigating how aging alters immune responses following vaccination (France Vaccin 2030).

We are seeking postdoctoral fellows with experience in preclinical models, flow cytometry, and immune labeling (IF/IHC).

Keywords:
Respiratory infections, Post-acute Infection Syndromes, HIV/AIDS, Emergent Virus, Myeloid cells, immune reprogramming, Aging, Gut microbiota, Cellular senescence, Pro/prebiotics, Senolytics, Therapy, Vaccine.