Prof. Thierry Calandra, Full Professor
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Medicine Department CHUV |
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Research activities :
- Innate immunity, host genetics and infectious diseases
Research key words :
- Innate immunity, infectious diseases, sepsis, Macrophage migration inhibitory factor, Toll-like receptors.
Innate immunity, infectious diseases, sepsis, Macrophage migration inhibitory factor, Toll-like receptors.
Microbial sensing and killing or walling off invasive pathogens are key features of the immune system. Recognition of microbes or activation of cells by danger signals (foreign harmful compounds or endogenous molecules) are mediated by families of pattern-recognition molecules including the complement system, Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors and C-type lectins.
The recognition of pathogens by innate immune cells activates a series of intracellular events resulting in the initiation of an inflammatory response, characterized by the release of a broad spectrum of immunodulatory mediators such as cytokines that helps to contain the infection and to activate of the adaptive immune response.
Dysregulated innate immune reactions have dramatic consequences for the infected host, as observed in patients with sepsis. Indeed, Sepsis remains one of the leading causes of mortality worldwide. Our understanding of the pathogenesis of sepsis has improved markedly in recent years. Unfortunately, new treatment strategies only modestly increased survival of critically ill septic patients.
To identify new therapeutic targets for the treatment of septic patients, we need to improve our knowledge of the molecular mechanisms governing host-pathogen interactions and innate immunity. Furthermore, it is well established that genetic factors influence the development of the inflammatory and innate immune responses to microbial challenge.
Combining basic and applied research is required to better understand the role played by innate immunity and genetic host variants in the course of severe infections. Our translational approach has the potential to identify new pathogenetic factors and therapeutic targets for septic patients, thereby linking basic research to patient care. Our main goals are to :
- Characterize the innate immune pathways activated by microbial pathogens (bacteria and fungi) and viral vaccine vectors in innate immune cells (macrophages and dendritic cells)
- Decipher the role of the pro-inflammatory cytokine macrophage migration inhibitory factor in the control of inflammatory and innate immune responses
- Identify genetic factors that influence the susceptibility to or the severity of infectious diseases,
- Develop new treatment startegies for the management of septic patients.
Our research team provides expertise in areas such as molecular and cell biology, experimental animal models, genetic epidemiology and biostatistics in a highly motivating university hospital environment.
Representative publications :
- Roger T et al. Histone deacetylase inhibitors impair innate immune responses to Toll-like receptor agonists and to infection. Blood. 2011, 117(4):1205-17.
- Roger T et al. Protection from severe Gram-negative sepsis by targeting Toll-like receptor 4 (TLR4). Proc. Natl. Acad. Sci. U.S.A. 2009, 106:2348-52.
- Delaloye J et al. Cross-activation of TLR2-TLR6, MDA-5 and NALP3 imflammasome for innate immune sensing of Modified Virus Ankara (MVA). PLoS Pathogens 2009, Jun;5(6):e1000480
