Figure 6

Toll-like receptors are innate pattern recognition receptors which identify the pathogen-associated molecular patterns (PAMPs) of specific pathogens. For example, TLR4 recognizes the immunologically active cell wall pattern of gram-negative bacteria, lipopolysaccharide (LPS), which is also found on E. coli. The role of these receptors has recently expanded to include the broader recognition of “danger” associated molecular patterns (DAMPs). These include a novel subset of proteins that are produced and released by nearby cells undergoing cell death or distress, known as alarmins, which are putatively recognized by TLRs, including both TLR4 and TLR2. Proteins that have been identified as alarmins thus far include hyaluronan, Heat Shock Proteins, and high mobility group box (HMGB) 1. In addition, the list of exogenous or environmental factors that are hypothesized to activate TLR4 (directly or indirectly) is ever-expanding. These include drugs of abuse (e.g. opiates, amphetamines, and ethanol), saturated dietary fats, and other toxins (e.g. air pollution).