Immunopathogenesis
of viral infections
and immune aging

Delphine Sauce

Team Leader :

Sauce Delphine

Contact the team

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.

VIH VIH
Représentation d’un des biomarqueurs étudiés dans l’équipe Représentation d’un des biomarqueurs étudiés dans l’équipe
Erosion des télomères, signe de vieillissement Erosion des télomères, signe de vieillissement
Coronavirus Coronavirus

The team members

Sauce Delphine

Sauce Delphine

Team Leader

Boddaert Jacques

Boddaert Jacques

PU-PH, Pitié Salpêtrière Hospital

Lacroix Lætitia

Lacroix Lætitia

(design engineer)

Chauvin Manon

Chauvin Manon

PhD student

Cohen-Bittan Judith

Cohen-Bittan Judith

PH, Hôpital Pitié Salpétrière

Gutierrez Melo Nicolas

Gutierrez Melo Nicolas

M2 student

Khiami Frédéric

Khiami Frédéric

PU-PH, Hôpital Pitié Salpétrière

Minaud Alix

Minaud Alix

M2 student

Vallet Hélène

Vallet Hélène

MCU-PH, Hôpital St Antoine

Pedruzzi Eric

Pedruzzi Eric

IR Inserm

Our research focus on 3 axes

  • Immunosenescence
  • Inflammation & acute stress
  • Biomarkers
  • Viral Infections
  • Translational research
  • Human Immunology

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

1.

Larsen M, Bayard C, Lepetitcorps H, Cohen-Bittan J, Appay V, Boddaert J, Sauce D. Elevated Neopterin Levels Predict Early Death in Older Hip-fracture Patients. EBioMedicine. 2017 Dec;26:157-164.

2.

Fali T, Fabre-Mersseman V, Yamamoto T, Bayard C, Papagno L, Fastenackels S, Zoorab R, Koup RA, Boddaert J, Sauce D*, Appay V*. Elderly human hematopoietic progenitor cells express cellular senescence markers and are more susceptible to pyroptosis. JCI Insight. 2018 Jul 12;3(13):95319.

3.

Fali T, Papagno L, Bayard C, Mouloud Y, Boddaert J, Sauce D*, Appay V*. New Insights into Lymphocyte Differentiation and Aging from Telomere Length and Telomerase Activity Measurements. J Immunol. 2019 Apr 1; 202 (7): 1962-1969.

4.

Fastenackels S, Bayard C, Larsen M, Magnier P, Bonnafous P, Seddiki N, Appay V, Gautheret-Dejean A, Sauce D. Phenotypic and Functional Differences between Human Herpesvirus 6- and Human Cytomegalovirus-Specific T Cells. J Virol. 2019 Jun 14;93(13):e02321-18.

5.

Vallet H, Bayard C, Lepetitcorps H, O’Hana J, Fastenackels S, Fali T, Cohen-Bittan J, Khiami F, Boddaert J, Sauce D. Hip Fracture Leads to Transitory Immune Imprint in Older Patients. Front Immunol. 2020 Sep 18;11:571759.