Innate immune recognition of microbial infection

Vaccination relies on presenting the innate immune system with molecular patterns characteristic of a given microbial pathogen, with the specific purpose of inducing future protective immunity against that pathogen. Although several good vaccines exist that protect humanity against historically significant microbial pathogens, many of these vaccines were empirically derived without precise knowledge of the molecular mechanisms that make them so successful. Thus, in the face of new microbial threats, such as the most recent outbreaks of H5N1 Influenza A viruses in avian and human populations, we are reminded of the real challenges we face in designing optimal protective vaccines. Importantly, certain poorly characterized aspects of natural infection (not incorporated in most vaccines) are particularly effective in inducing the right combination of signals for generating immune memory. We are interested in discovering innate immune signaling modules that sense new and universal pathogen associated molecular patterns specifically within the context of natural infections. We have devised an experimental system to define and delineate the nature of these signals and the pattern recognition pathways they trigger.