chapter  3
20 Pages

Analysis of TLR Expression, Regulation, and Signaling

ByHui Xiao, Xiaoxia Li, Derek W. Abbott

References ................................................................................................................ 55

The innate immune system recognizes and responds to pathogenic organisms. In doing so, this system is responsible for initiating a cytokine response designed to tailor the adaptive immune system to eradicate the offending organism. Because this initial cytokine release must be tightly regulated, signal transduction pathways leading to this cytokine release are highly coordinated. This coordination begins at the cell surface with the initial recognition of pathogens by Toll-like receptors (TLRs). TLRs recognize components of bacteria, fungi, or viruses (collectively called pathogen-associated molecular patterns, or PAMPs) and play a major role in host defense against infection.1 The majority of the TLR family members are abundantly expressed in monocytes, macrophages, and dendritic cells.2 These receptors activate a highly conserved signaling network and ultimately lead to the activation of a variety of transcription factors, including NF-κB, ATF2, c-JUN, and IRF3/7. These transcription factors then act in synergy to induce the expression of hundreds of cellular genes.3