The Dual Complexity of PTX3 in Health and Disease: A Balancing Act?

The humoral arm of innate immunity is complex and includes various molecules that serve as markers of inflammation with complementary characteristics, such as the short pentraxins C-reactive protein (CRP) and serum amyloid P (SAP) and the long pentraxin PTX3. There is a growing amount of evidence - including mouse and human genetics - that suggests that PTX3 is essential in conferring host resistance against selected pathogens and, moreover, that it plays a dual antagonistic role in the regulation of inflammation. Dissection of such a yin-and-yang role of pentraxins in immunity and inflammation is timely and significant as it may pave the way for better clinical exploitation against various diseases. The long pentraxin PTX3 is an essential component of humoral innate immunity and plays a role in the regulation of inflammation.PTX3 has complex effects on the vasculature, including an interaction with the angiogenic growth factor FGF2 and the regulation of vessel wall tone.By modulating complement-driven inflammation, PTX3 acts as an oncosuppressor gene in mice and selected human tumors.By interacting with provisional matrix components, PTX3 contributes to the orchestration of wound healing and tissue repair/remodeling.PTX3 and the related pentraxins C-reactive protein (CRP) and serum amyloid P (SAP) can exert dual roles in inflammation and antimicrobial resistance, by either exerting a protective function or amplifying tissue damage.Dissection of the yin-yang role of pentraxins in immunopathology may pave the way towards better exploitation of these molecules as envisaged disease markers and candidate therapeutic agents.