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Tissue inflammation is responsible for significant morbidity and mortality in humans. Originally thought to be restricted to acute or chronic infection or autoimmune diseases, it is becoming increasingly clear that tissue inflammation is associated with a high proportion of most chronic diseases in humans. Inflammation is a consequence of the activation of pattern recognition receptors of the innate immune response. Following their activation, effector mechanisms are triggered and adaptive immunity ensues. I will discuss the role that these pathways play with emphasis on the increasingly important contribution that is recognized for the components of the NLR inflammasome proteins. We find that these contribute to an astonishingly wide spectrum of human inflammatory diseases. As a result, therapeutic intervention in this area holds promise for treatment of human disease.