Complement is an important innate immune defense machinery and plays crucial roles in infection and inflammation. Today, the complement is not only a driver of innate immunity, its functions even extend to additional physiological and/or pathophysiological roles in immune surveillance and homeostasis. The complement exerts its functions through effective rules of activation and regulation under precise control of balance. However, if dysregulated, the complement often leads to pathophysiological situations.
Pentraxins are a superfamily of pattern recognition molecules characterized by a cyclic multimeric structure and a conserved pentraxin signature. Based on the primary structure of the subunit, the pentraxins are defined as short pentraxins (C-reactive protein, CRP; serum-amyloid P component, SAP) or long pentraxins (pentraxin 3, PTX3; pentraxin 4, PTX4; neuronal pentraxin 1, NP1; neuronal pentraxin 2, NP2; neuronal pentraxin receptor, NPR). The pentraxins are involved in both complement activation and regulation, thus diversify the immune effector functions and further restrict overwhelming inflammation.
The complement system is a double-edged sword, playing a key role in the elimination of danger signals and hostile intruders, but also being responsible for immunopathology when massively activated or improperly controlled. Pentraxins are involved in both complement activation and regulation via crosstalk with major complement initiating molecules as well as complement regulators. The crosstalk events between the pentraxins and the PRMs involved in complement activation synergize their roles in immunosurveillance, anti-microbial immune responses, and immunologic homeostasis. However, these cooperative events may also lead to immunopathogenicity in infection and inflammation if activated inappropriately. Pentraxins-mediated complement activation and regulation may also influence and thus contribute to chronic inflammation, which likely constructs a microenvironment for initiation and development of complement-mediated pathology. The beneficial and pathogenic side of the potential functional roles of pentraxins and their involvement in complement activation and regulation need to be further explored. Whether it is involved in potent inducers of immunopathology during infection and inflammation and how it exacerbates disease severity are also intriguing unanswered questions.
This Research Topic aims to gain an insight into the functional roles of the pentraxins in infection and regulation of inflammatory responses with a focus on the interaction with the complement system. We welcome the submission of manuscripts including Original Research, Review, Mini-Review, Perspective, Commentary, and Opinion articles types that cover, but are not limited to, the following topics:
1) Biochemical interactions between pentraxins and complement
2) Role of the pentraxins in complement activation, regulation, and crosstalk
3) Interaction of pentraxins and complement in infections
4) Interaction of pentraxins and complement in vascular pathology
5) Interaction of pentraxins and complement in cancer
Dr. Garlanda is the inventor of the patent (EP20182181) on pentraxin-3 . The other Topic Editors declare no conflict of interest with regards to the Research Topic theme.