Our lab studies the complex relationship between immune cells and viruses. Our projects are at the interface between cell biology, immunology and virology.
- How the innate immune system senses the presence of viruses at the molecular level.
Evolutionarily conserved molecular patterns on microbes are recognized by Pathogen Recognition Receptors to induce a potent innate immune response and a tailored adaptive immune response. A subset of the Toll-Like Receptors (TLRs) specific for molecular patterns on nucleic acids are located in the endosome. Microbial nucleic acids are generally not directly accessible to cell surface receptors. They are present in apoptotic bodies of infected cells or can be exposed upon degradation of the microbes within the endocytic pathway. Therefore it is critical that nucleic acid-sensing TLRs bind their ligands and signal from the endocytic/phagocytic pathway. Endosomal TLRs have a poor intrinsic ability to discriminate between host- and pathogen-derived ligands and are therefore tightly regulated all along their intracellular trafficking. Elucidating at the molecular level how these TLRs are precisely directed into the compartments that define their downstream signaling will enable us to better understand their biology and help modulate their activity during immunotherapeutic strategies.
- HIV and macrophages: a complex relationship.
Macrophages are critical for the detection of pathogens and can deal with many of them. However in the case of HIV, macrophages are used by the virus, which efficiently infects them and makes them produce new virions. HIV-infected macrophages can survive in many tissues and accumulate intracellular stocks of infectious HIV. HIV-infected macrophages represent therefore an important viral reservoir that should be treated to cure patients from HIV. Macrophages accumulate newly synthesized viral particles in internal compartments, the VCCs or Virus Containing Compartments. The VCC nature and origin remain elusive and very little is known about the molecular mechanisms allowing viral assembly and production.
Our general aim is to decipher at the molecular level how incoming HIV is sensed, how macrophages react to HIV, how HIV escapes this control and succeeds to replicate into macrophages. We are also developing new strategies to target these viral reservoirs.