Effects of differences in lipid A structure on TLR4 pro-inflammatory signaling and inflammasome activation

Abstract

The vertebrate immune system exists in equilibrium with the microbial world. The innate immune system recognizes pathogen-associated molecular patterns via a family ofToll-like receptors (TLR) that activate cells upon detection of potential pathogens. Because some microbes benefit their hosts, mobilizing the appropriate response, and then controlling that response is critical in the maintenance of health.TLR4 recognizes the various forms of lipid A produced by Gram-negative bacteria. Depending on the structural form of the eliciting lipid A molecule, TLR4 responses range from a highly inflammatory endotoxic response involving inflammasome and other pro-inflammatory mediators, to an inhibitory, protective response. Mounting the correct response against an offending microbe is key to maintain-ing health when exposed to various bacterial species. Further study of lipid A variants may pave the way to understanding how TLR4 responses are generally able to avoid chronic inflammatory damage. © 2012 Chilton, Embry and Mitchell.