Using innate immunity to characterize the host response to microbial invasion in severe sepsis

Severe sepsis is a life-threatening systemic inflammatory response to microbial infection. Although mortality from severe sepsis has decreased modestly over the past three decades, its incidence is increasing dramatically. Current treatment of severe sepsis relies primarily on identification and appropriate antibiotic coverage of the invading pathogen, with supportive therapies aimed primarily at reducing the risk of associated organ injury. Current efforts to identify the invading pathogens are successful in approximately only 50% of patients with severe sepsis. In this review, we examine host-pathogen interactions through the Toll-like receptors and Nod signaling systems as principal mechanisms of the innate immune response, and explore the application of high-throughput genomic technologies that have permitted a more complete dissection of the innate immune response during severe sepsis. Early controlled studies suggest that these genome-wide tools can readily identify pathogen-specific host responses in macrophages and dendritic cells. However, despite considerable progress, clinical application of these approaches to pathogen recognition in hospitalized patients with severe sepsis is still years away.