Several plasma proteins that recognize microbial structures and participate in innate immunity belong to the pentraxin family, which is a phylogenetically old group of structurally homologous pentameric proteins. Prominent members of this family include the short pentraxins, C-reactive protein (CRP) and serum amyloid P (SAP), and the long pentraxin PTX3. Both CRP and SAP bind to several species of bacteria and fungi. The ligands recognized by CRP and SAP include phosphorylcholine and phosphatidylethanolamine, respectively, which are found on bacterial membranes and become exposed on apoptotic cells. CRP, SAP, and PTX3 all activate the classical pathway of complement by binding C1q.
Plasma concentrations of CRP are very low in healthy individuals but can increase up to 1000-fold during infections and in response to other inflammatory stimuli. The increased CRP levels result from increased synthesis by liver cells induced by the cytokines IL-6, IL-1, and TNF, which are produced by phagocytes and DCs as part of the innate immune response to infections or injury. Liver synthesis and plasma levels of several other proteins, including SAP and some unrelated to the pentraxins, also increase in response to IL-1, IL-6, and TNF. All of these plasma proteins are called acute-phase proteins because they are elevated in the blood during acute inflammatory reactions, and their increased production is part of the acute-phase response to infection and other insults.
PTX3 is produced by several cell types, including DCs, macrophages, and endothelial cells, in response to TLR ligands and inflammatory cytokines, such as TNF, and may be considered an acute-phase reactant. PTX3 is also stored in neutrophil granules and released as neutrophils die. PTX3 recognizes various molecules on fungi, certain bacteria, and viruses, as well as apoptotic cells, and activates the classical complement pathway. Studies with knockout mice reveal that PTX3 provides protection against several microbes, including the fungus Aspergillus fumigatus and the influenza virus.
