Systems biology strives to derive comprehensive and accurate descriptions of complex systems such as the innate immune system. The innate immune system is essential for host defense and is responsible for early detection and containment of pathogens, yet the resulting inflammatory response is a double-edged sword that must be tightly regulated. Our current understanding indicates that the innate immune system is controlled by complex regulatory networks, which contain cross-talk, insulation, feedback loops, signal amplification, integration and dampening. Such dynamic behavior and complexity are essential to innate immunity, and critical for maintaining homoeostasis and accurately distinguishing pathogenic microbial infections from harmless threats. We focus this review on Toll-like receptor regulation of innate immune response to microbial pathogens, and emphasize recent studies using high throughput technologies and computational approaches in this field. The eventual integration of global molecular and interaction data into predictive models will provide the necessary foundation to cultivate a systems level understanding of innate immunity.
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