Fig. 1

Activity of PTX3 in innate immunity. PTX3 represents the humoral arm of the innate immunity. Inflammatory cytokines, Toll-like receptors (TLRs), microorganisms and microbial moieties stimulate secretion of PTX3 by polymorphonuclear (PMN) neutrophils, macrophages, and dendritic cells. (1) Release of PTX3 by PMN neutrophils occurs quickly and casts an immediate defensive response. In fact, these cells possesscytosolic granules containing a stored, ready- to-release, pool of PTX3. (2) Macrophages and dendritic cells are other effectors of the innate immunity, which neo-synthesize PTX3 upon stimulation. This newly synthesized pool of PTX3cells is responsible for a slower response to infective agents, which might persist even several days. Released PTX3 regulates inflammatory reactions by acting through several pathways/mechanisms: I) PTX3 released by PMN neutrophils localizesat level of neutrophil extracellular traps (NETs). NETs represent an extracellular fibrillary network, where some nuclear components, such as DNA and histones, are variously assembled with bactericidal proteins, such as azurocidin1(AZU1) andmyeloperoxidase(MPO). Within NETs, PTX3 and anti-microbial molecules converge and cooperate to enhance binding and killing of infective agents. II) PTX3 released in the extracellular space binds to specific microbial ligands and activates the complement cascade through interaction with C1q particles (classical pathway) or ficolins and mannose-binding lectins (lectin-mediated pathway). PTX3-induced complement activation enhances the inflammatory response. III) Finally, extracellular PTX3 opsonizes microorganisms binding to specific molecules on the cell surface (i.e. zymosan on Aspergillusfumigatus) and, in turn, it is recognized by Fcgamma receptors expressed by phagocytic cells, thus promoting microbial clearance. The interaction of PTX3with Fcgamma receptors indicates the antibody-like function of PTX3 and underlies its functional overlapping between innate and adaptive immunity during inflammation. (FcγR Fcgamma receptor, IL-1 interleukin-1, LPS lipopolysaccaride, PTX3 pentraxin 3, TNF-alpha tumor necrosis factor-alpha)