The ability to detect pathogens is an essential component of the immune system. The first line of sensing is stimulated by the recognition of molecules present in bacteria, viruses and parasites but not found in the host. These molecules are accessible for binding by germ line-coded host receptors. Binding activates a broad specificity inflammatory response characterised by the recruitment and activation of phagocytes and the production of antimicrobial compounds. This constitutes the innate immune response that in its turn will trigger acquired immunity. Acquired immunity comes in the late phase of infection, is specific and creates immunological memory. Acquired immunity is present only in higher chordates. All other species rely on innate defences to fight off infection. Thus, innate immunity is considered as the prototypical immune defence and is well conserved among species from plants and fruit flies to mammals.

The importance of innate immunity for adaptive responses has implications in the treatment of infectious diseases. Understanding the initial stages of pathogen recognition and their link to subsequent signalling is crucial for manipulating host defences in the face of life-threatening tissue damage (sepsis).

Mechanisms causing sepsis are highly conserved from fruit flies to humans. It is consequently an extremely pertinent question in both immunological research and clinical intervention to ask how initial stages of pathogen sensing are achieved.

We would like to address a set of interrelated questions on the initial recognition of pathogens by innate host sensors. Genetic studies have provided some insights into these matters but a combination of biochemical and cell biological studies are now needed to further our understanding.
Firstly, how do multiple host receptors synergise to achieve recognition?
Secondly, are host receptor complexes formed on pathogens or is there detection of exported/recycled material?
Thirdly, can small molecules resembling bacterial cell wall components be exploited to trigger or suppress innate immunity?
Lastly, how does the immune response integrate in the homeostatic mechanisms of an individual during adult life?