Cell Biology, Host-Pathogen Interactions Department

Department head : Claudine PIQUE
Assistants department heads : Alexandre BENMERAH and Claire POYART

The Department of “Cell Biology and Host-Pathogens Interactions” includes 8 teams and 1 group Institut Cochin sharing a common interest in the exploration of the interactions between the organism or the host cell and different pathogens – bacteria, parasites or viruses.

Intracellular pathogens not only exploit their host cell environment to ensure their own propagation, but also modulate host cell functions and in many cases, display multiple strategies to counteract host-defence mechanisms. The cross-exploration of the cellular and molecular aspects of pathogenesis has therefore, emerged as a key approach in infectious disease research. This idea has motivated the creation of the “Cell Biology and Host-Pathogen Interactions” department, which associates scientists and clinicians specialized in virology, bacteriology, parasitology and immunology to scientists initially trained in basic cell biology.

Major axes of Research:

• Interactions between human retroviruses and host cells (Teams: S. Bénichou & A. Benmerah, C. Berlioz-Torrent & S. Emiliani, S. Bourdoulous & F. Niedergang, F. Margottin-Goguet and C.Transy, C. Pique, group Institut Cochin M. Bomsel, )

These researches essentially focus on Human Immunodeficiency Virus type 1 (HIV-1) and cover all aspects of the HIV-1 life cycle. For the early steps, the teams will explore HIV-1 interaction with mucosal targets, the trafficking of the entry co-receptor CCR5, and the roles of auxiliary viral proteins or cellular proteins in post-entry and nuclear events. For the late steps, the intracellular trafficking of viral proteins and the network of viral and cellular proteins involved in viral particle assembly will be unravelled and how HIV-1 alters the functions of macrophages will be also investigated. HTLV-1/host relationships will be also studied through the identification of new cell partners of viral proteins.

• Interactions between bacteria and host cells (Teams: S. Bourdoulous & F. Niedergang, J.D. Chiche, C. Poyart and I. Tardieux).

Modulation of cell signaling pathways by Neisseria meningitidis to promote its uptake and escape immune response, the mechanisms of epithelium invasion by group B Streptococcus and the determinants of their virulence as well as the roles of the Toll-like receptor in cell response to Gram-positive bacteria will be investigated.

• Interactions between parasites and host cells (Teams: G. Langsley, C.Poyard and I. Tardieux)

The contribution of vesicular trafficking of Plasmodia to parasite survival within erythrocytes, the way by which Theileria subverts host cell signalling pathways in leukocytes and the molecular mechanisms involved in tissue invasion by Toxoplasma, notably the contributions of parasite and host cell actin cytoskeleton, will be explored.

• Basic aspects of cell trafficking (Teams: S. Bénichou & A. Benmerah, S. Bourdoulous & F. Niedergang)

These researches will explore endocytosis, including the role of clathrin coats in internalization and endosomal sorting and the mechanisms of uptake in specialized immune cells such as macrophages and dendritic cells, with emphasis on the intracellular trafficking and membrane remodeling and cytoskeletal reorganizations.

• Clinical projects (Teams: J.D. Chiche, G. Langsley, C. Poyart and I.Tardieux, group Institut Cochin M. Bomsel)

Two large-scale evaluations will be performed to analyze the polymorphisms of innate immunity genes on the susceptibility to- and the severity of- pulmonary infections and the prevention of group B streptococcal neonatal infections. Anti-pathogen strategies will be also conducted, including the development of a mucosal vaccine or microbicides to inhibit HIV-1 transmission and of a new anti-malaria drug based on a lead inhibitor compound to P. falciparum protein kinase A.