Opsona at leading edge of innate immunity research

Innate immune system

The innate immune system has recently been described as the “executive” of the immune system. It was the discovery of the first Pattern Recognition Receptors (PRRs), the TLRs, that led to an explosion of research in the innate immune system in the late 1990s.

The 10 human TLRs each have specificity to ligands from pathogens, which then stimulate a network of signalling pathways culminating in the targeted production of a multitude of pro-inflammatory mediators. (cytokines) The cytokine profile is contingent on the original trigger (eg. a viral ligand produces a different profile to bacterial). These cytokines then direct the appropriate adaptive immune response (cytotoxic killing and/or B-cell memory response). 

Endogenous danger signal

The scientific community has now accepted that inflammatory and autoimmune diseases involve PRRs including the TLRs, Nods and Inflammasome. The "endogenous danger signal" hypothesis has led to an increased understanding of what drives inflammatory diseases.

Danger signals can take the form of pathogen products located at the site of inflammation (e.g.  pathogen ligands have been identified in the joints of arthritis patients or in atherosclerotic plaques), products of tissue degradation (e.g. hyaluronic acid, heparan sulphate, fibronectin, double stranded RNA) or necrotic cell debris (eg. HMGB1, heat shock proteins). 

The understanding of what drives the innate immune system in inflammatory diseases is rapidly evolving. Opsona’s founders and collaborators are at the forefront of this research.

Targeting TLRs

The TLRs and Inflammasome signalling pathways represent significant targets for therapeutic intervention in the case of autoimmune diseases. The value in targeting at the level of the TLRs and Inflammasome signalling is clear:

  • Targeting at the cause of the disease, which are upstream to the pro-inflammatory mediators  (ie. TNF- α, Interferons, IL-1, IL-6, IL-8 etc)
  • The higher in the pathway you target, the more mediators you prevent from being released, reducing the amount of damage