Dr. Caroline Demangel

Dr. Caroline Demangel (Institut Pasteur) received her PhD from the National Institute of Agronomy Paris-Grignon in 1991 then pursued her training as a post-doctoral researcher at the Centenary Institute of Sydney, Australia, working on the development of anti-tuberculous vaccines. She now directs the Immunobiology of Infection Research Unit at the Institut Pasteur, Paris, France. Her lab studies the mechanisms employed by pathogenic mycobacteria to evade immune responses, with a particular focus on Mycobacterium leprae and ulcerans, the causative agents of Leprosy and Buruli ulcer, respectively.

To establish host residence these bacteria have evolved complex lipids that are strategically located at the interface with the immune system and play dual roles in bacterial virulence and host immunomodulation. The main goal of C. Demangel’s group is to identify the molecular mechanisms by which such lipids operate and to translate this basic knowledge into better treatments against mycobacterial infections. Lepromatous leprosy, the most severe manifestation of leprosy, is characterized by poor cellular responses and uncontrolled proliferation of the bacilli throughout the skin. The lack of inflammatory infiltrates around heavily infected macrophages in lesions suggests that M. leprae evades immune recognition. Among the molecules suspected to be critical in this process is the phenolic glycolipid 1 (PGL-1), a compound produced specifically by M. leprae.

Until recently, studies on the biological function of PGL-1 were limited by the inability to grow M. leprae in vitro and to genetically engineer this bacterium. Using a recombinant M. bovis BCG displaying PGL-1 in the cell envelope, C. Demangel’s lab contributed to show that PGL-1 confers capacity to exploit complement receptor 3 (CR3) for efficient invasion of human macrophages and evasion of inflammatory responses. Current work aims at deciphering which signaling pathways are impacted, and what are the consequences of this interaction on immune cell functions.

Recent publications include:
Guenin-Macé, L., Siméone, R. and Demangel, C. (2009) Lipids of pathogenic mycobacteria: Contributions to virulence and host immune suppression. Transbound Emerg Dis. 56, 255-268.
Tabouret, G., Astarie-Dequeker, C., Demangel, C., Malaga, W., Constant, P., Ray, A., Honoré, N., Fatimath Bello, N., Perez, E., Daffé, M. and Guilhot, C. (2010) Mycobacterium leprae phenolglycolipid-1 expressed by engineered M. bovis BCG modulates early interaction with human phagocytes. PLoS Pathogens, 6(10):e1001159.