Microbiota & Immune trajectories
Establishing the impact of chronic infections and inflammation in immunosenescence is relevant to our understanding of its consequences for the health of older people.
The study of the ageing immune system is a growing area of research, but our knowledge of the cellular and molecular changes underlying the decline in immune function with age remains limited.
We are therefore conducting comparative studies of immunological and inflammatory attributes in settings with signs of immune ageing, including advanced age, certain viral infections, and reduced thymic activity.
We learn from each of these models to better understand immune ageing.
- Immunosenescence
- Inflammation & acute stress
- Biomarkers
- Viral Infections
- Translational research
- Human Immunology
HIV
Representation of one of the biomarkers studied by the team
Telomere erosion, a sign of ageing
Coronavirus
Host immunity is installed in early-life perfectly synchronized with initial colonization of the human gut. We study the interactions between environmental exposure, gut microbiota and host immunity to understand healthy gut microbiota homeostasis and human physiopathology. We aim to decipher the role of adaptive immunity on gut microbiota homeostasis, with particular emphasis on microbiota-specific immunoglobulin A (immuno-microbiota).
We seek to identify antibody targets and quantify dietary metabolites with immune-modulatory properties and associate them with gut microbiota composition and immune-microbiota profiles.
We will disentangle microbial, environmental and immunological interactions in <em>in vitro</em> intestinal barrier models to unravel mechanistic insights concerning the effect of microbes on gut barrier integrity. We finally aim to investigate if aberrant gut microbiota composition and/or gut immunity may be associated with human pathophysiology spatially distant from the gut, such as obesity and allergy.
- Translational research
- Metagenomics
- Secretory IgA
- Immuno-microbiota
- Ecology
- Intestinal barrier
intestinal bacteria, gut microbiome helps control intestinal digestion and the immune system
infant gut microbiome, the genetic material of all microbes
The team members
Our research focus on 3 axes
1. Immune aging & antiviral responses
Characterisation of immunosenescence:
Life expectancy in Europe has almost doubled in the last century. Nowadays, it is common to live beyond the age of 75. However, advanced age is often accompanied by an increase in chronic diseases, leading to a significant decline in quality of life. This phenomenon, known as immunosenescence, is thought to be directly related to the decline of the immune system with age, which makes individuals more susceptible to disease and increases morbidity and mortality.
Since the accumulation of functionally impaired leukocyte populations and the loss of naive immune cells have been described as the main feature of an ageing and weakened immune system, we aim to further characterise the subtypes affected by age and/or CMV infection. This will determine an immune signature encountered in ageing that may help clinicians to define vulnerable patients.
2. Regulation of host-pathogen relationships
Impact of stress on the immune system:
Physiological ageing is associated with alterations in the immune system within the innate and adaptive compartments. Many links exist between stress and immunity, leading to high levels of inflammation, which are necessary to defend one’s integrity but which must be controlled in order to maintain immune balance. Older people are not equal in the face of stress, particularly because of the great inter-individual variability in terms of immune reserve.
A better understanding of the interactions between stress and immunity could allow us to understand the mechanisms involved in the impact of the immune system on resilience after acute stress in the elderly, but also to consider targeted therapies specific to alterations in the immune system in order to improve the prognosis and the management of patients. We are studying these interactions in different acute clinical situations: 1) during a trauma frequently encountered in the elderly: fracture of the upper end of the femur; 2) during a viral infection (influenza and Covid-19); 3) during admission to the intensive care unit (sepsis).
3. Clinical immunology and therapeutic strategies
Immune resource depletion and the role of chronic immune activation:
The main role of haematopoietic stem cells (HSCs) and progenitor cells (PCs) is to produce and replenish the various pools of white and red blood cells.
Under conditions of cumulative stress during life, HSCs exhibit several defects, related to altered metabolism, increased cell death and senescence, eventually contributing to the loss of regenerative and differentiation potential of stem cells, and the decline of immune competence in the elderly. Here, we aim to determine the intrinsic factors that regulate HSC and progenitor deficiencies in the elderly.
This knowledge identifies new therapeutic targets that we are testing to improve the functions of haematopoiesis and thus limit ageing.
The opportunities
- Participation in clinical trials
- Validation of biomarkers (predictive and prognostic)
- Identification of new targets in physiological and pathological ageing
- Regenerative medicine
- International network of collaborators
Publications
Primary immune responses are negatively impacted by persistent herpesvirus infections in older people: results from an observational study on healthy subjects and a vaccination trial on subjects aged more than 70 years old. EBioMedicine. 2022 Feb;76:103852. doi: 10.1016/j.ebiom.2022.103852. Epub 2022 Feb 1. PMID: 35114631 Free PMC article.
Clinical, Virological and Immunological Subphenotypes in a Cohort of Early Treated HIV-Infected Children. Front Immunol. 2022 May 3;13:875692. doi: 10.3389/fimmu.2022.875692. eCollection 2022. PMID: 35592310 Free PMC article.
Mechanisms of immune aging in HIV. Clin Sci (Lond). 2022 Jan 14;136(1):61-80. doi: 10.1042/CS20210344. PMID: 34985109 Review
LOX-1-Expressing Immature Neutrophils Identify Critically-Ill COVID-19 Patients at Risk of Thrombotic Complications. Front Immunol. 2021 Sep 20;12:752612. doi: 10.3389/fimmu.2021.752612. eCollection 2021. PMID: 34616409 Free PMC article.
Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients. Front Cell Infect Microbiol. 2021 Aug 23;11:709893. doi: 10.3389/fcimb.2021.709893. eCollection 2021. PMID: 34497777 Free PMC article.
Distinct cytokine profiles associated with COVID-19 severity and mortality. J Allergy Clin Immunol. 2021 Jun;147(6):2098-2107. doi: 10.1016/j.jaci.2021.03.047. Epub 2021 Apr 22. PMID: 33894209 Free PMC article.
Immune activation and chronic inflammation: Is there an additional effect of HIV in a geriatric population? Medicine (Baltimore). 2021 Apr 30;100(17):e25678. doi: 10.1097/MD.0000000000025678. PMID: 33907138 Free PMC article.
Hip Fracture Leads to Transitory Immune Imprint in Older Patients. Front Immunol. 2020 Sep 18;11:571759. doi: 10.3389/fimmu.2020.571759. eCollection 2020. PMID: 33072114 Free PMC article.
Phenotypic and Functional Differences between Human Herpesvirus 6- and Human Cytomegalovirus-Specific T Cells. J Virol. 2019 Jun 14;93(13):e02321-18. doi: 10.1128/JVI.02321-18. Print 2019 Jul 1. PMID: 30996090 Free PMC article.
New Insights into Lymphocyte Differentiation and Aging from Telomere Length and Telomerase Activity Measurements. J Immunol. 2019 Apr 1;202(7):1962-1969. doi: 10.4049/jimmunol.1801475. Epub 2019 Feb 8. PMID: 30737273 Free article.
Impact of stress on aged immune system compartments: Overview from fundamental to clinical data. Exp Gerontol. 2018 May;105:19-26. doi: 10.1016/j.exger.2018.02.007. Epub 2018 Feb 7. PMID: 29427753 Free article.