Inflammation versus pattern recognition in the priming of anti-viral adaptive immune responses

Successful priming of adaptive immune responses is crucially dependent on innate activation signals that convert resting antigen-presenting cells (APCs) into immunogenic ones. APCs expressing the relevant innate pattern recognition receptors can be directly activated by pathogen-associated molecular patterns (PAMPs) to become competent to prime T-cell responses. Alternatively, it has been suggested that proinflammatory mediators synthesized by PAMP-exposed cells could activate APCs indirectly. However, data obtained with protein and peptide antigen + purified PAMP suggest that inflammatory signals cannot substitute for direct pattern recognition in APC activation for the priming of effector T cell responses. It is unclear whether the same is true under infectious conditions, or whether the sensing of infection-induced molecules such as IL-1 can replace pattern recognition. We are investigating this issue in infection models using influenza virus, lymphocytic choriomeningitis virus and other viral pathogens.