Extracellular pattern recognition molecules in health and diseases.

Abstract

The initiation of innate immune response relies on the recognition of pathogen-associated molecular patterns by pattern recognition molecules (PRMs), including the cellular pattern recognition receptors and extracellular soluble PRMs. Pattern recognition receptors such as Toll-like receptors (TLRs), NOD-like receptors and RIG-I like receptors are well documented cell-associated PRMs that sense microbial components on the cell surface, in the cytoplasm or in the nucleus of immune or non-immune cells to initiate the innate response to eliminate the invading pathogens.1,2 However, there is limited evidence of an extracellular PRM-mediated innate response to disease. In response to pathogen invasion, humoral PRMs are rapidly produced by a variety of cells and tissues, most notably by innate immune cells such as neutrophils, dendritic cells and macrophages. Extracellular humoral PRMs can be divided into different molecular families, primarily including pentraxins,3 collectins and ficolins.4 Accumulating evidence indicates that extracellular PRMs are important components of the humoral arm of innate immunity. They are able to recognize a variety of pathogenic agents and eliminate them through shared common mechanisms including complement activation, opsonization, agglutination, neutralization and regulation of inflammation (Figure 1). Moreover, extracellular PRMs also interact with cellular TLRs and regulate their function, jointly contributing to the recognition of microbial patterns and modulation of the innate immune responses.5,6,7,8