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01 Nov 2018

[Seminar] Rational Design of Immunomodulatory molecules targeting C-type lectins

Jérôme Nigou, from the Institut de Pharmacologie et de Biologie Structurale and French National Center for Scientific Research (CNRS) will be in Hong Kong on the 28th of November to give a talk in HKU Pasteur on:

Rational Design of Immunomodulatory molecules targeting C-type lectins

Abstract: Mycobacterium tuberculosis, the causative agent of tuberculosis, is one of the most effective human pathogens. It has evolved multiple molecular mechanisms to alter immune responses, including inflammation, thereby securing its colonization and survival inside the infected host. In particular, M. tuberculosis exposes specific glycolipids and lipoglycans at its cell envelope surface to target C-type lectin receptors (CLRs), DC-SIGN, Mannose Receptor or Mincle, expressed by innate immune cells, such macrophages and dendritic cells.The strategies used by M. tuberculosis to modulate the host inflammatory response prompted us to design synthetic molecules that mimic the bioactive structure of natural mycobacterial glycoconjugates, with the objective of developing innovative immunomodulatory compounds. To achieve this goal, we used a combination of approaches, including identification of the natural CLR agonist molecules present in the mycobacterial cell envelope, deciphering the molecular mechanisms of ligand-receptor interaction and bio-guided chemical synthesis. 

Dr Nigou will present the example of two fully synthetic families of molecules that display powerful activities in vitro and in vivo in mouse models: i) anti-inflammatory mannodendrimers, ligands of DC-SIGN, that prevent acute lung inflammation; ii) adjuvant glycolipids, ligands of Mincle, that induce strong Th1 and Th17 immune responses. These immunomodulatory compounds are currently tested in different pathologically models to determine the broader applicability of their therapeutic use.
 

Biosketch: Dr Jérôme Nigou is head of the team “Immunomodulation by Mycobacterial Lipids & Glycoconjugates” and of the Department “Tuberculosis & Infection Biology” at Institute of Pharmacology and Structural Biology (IPBS-CNRS, France). He has a strong background