https://www.journal-of-hepatology.eu/article/S0168-8278(16)00163-X/pdf

The pentraxins PTX3 and SAP in innate immunity, regulation of inflammation and tissue remodelling

Innate immunity includes a cellular and a humoral arm PTX3 is a fluid-phase pattern recognition molecule conserved in evolution which acts as a key component of humoral innate immunity in infectio

PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and Cancer

The first line of defense in innate immunity is provided by cellular and humoral mediators. Pentraxins are a superfamily of phylogenetically conserved humoral mediators of innate immunity. PTX3, the first long pentraxin identified, is a soluble pattern recognition molecule rapidly produced by several cell types in response to primary pro-inflammatory signals and microbial recognition. PTX3 acts as an important mediator of innate immunity against pathogens of fungal, bacterial and viral origin, and as a regulator of inflammation, by modulating complement activation and cell extravasation, and facilitating pathogen recognition by myeloid cells. In sepsis, PTX3 plasma levels are associated with severity of the condition, patient survival, and response to therapy. In combination with other established biomarkers, PTX3 could improve stratification of sepsis patients and thus, complement the system of classification and monitoring of this disease.

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The Long Pentraxin PTX3 as a Humoral Innate Immunity Functional Player and Biomarker of Infections and Sepsis.

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

The innate immune system is composed of a cellular arm and a humoral arm. Components of the humoral arm include members of the complement cascade and soluble pattern recognition molecules (PRMs). These PRMs recognize pathogen-associated molecular patterns and are functional ancestors of antibodies, playing a role in complement activation, opsonization and agglutination. Pentraxins consist of a set of multimeric soluble proteins and represent the prototypic components of humoral innate immunity. The prototypic long pentraxin PTX3 is highly conserved in evolution and produced by somatic and innate immune cells after proinflammatory stimuli. PTX3 interacts with a set of self, nonself and modified self ligands and exerts essential roles in innate immunity, inflammation control and matrix deposition. In addition, translational studies suggest that PTX3 may be a useful biomarker of human pathologies complementary to C-reactive protein. In this study, we will review the general functions of pentraxins in innate immunity and inflammation, focusing our attention on the prototypic long pentraxin PTX3.

The long pentraxin PTX3 as a key component of humoral innate immunity and a candidate diagnostic for inflammatory diseases.

Newborns and infants present a higher susceptibility to infection than adults, a vulnerability associated with deficiencies in both the innate and adaptive immune systems. Innate immune receptors are sensors involved in the recognition and elimination of microbes that play a pivotal role at the interface between innate and adaptive immunity. Pentraxin 3 (PTX3), the prototypic long pentraxin, is a soluble pattern recognition receptor involved in the initiation of protective responses against selected pathogens. Because neonates are generally resistant to these pathogens, we suspected that PTX3 may be provided by a maternal source during the early life times. We observed that human colostrum contains high levels of PTX3, and that mammary epithelial cell and CD11b+ milk cells constitutively produce PTX3. Interestingly, PTX3 given orally to neonate mice was rapidly distributed in different organs, and PTX3 ingested during lactation was detected in neonates. Finally, we observed that orally administered PTX3 provided protection against Pseudomonas aeruginosa lung infection in neonate mice. Therefore, breastfeeding constitutes, during the early life times, an important source of PTX3, which actively participates in the protection of neonates against infections. In addition, these results suggest that PTX3 might represent a therapeutic tool for treating neonatal infections and support the view that breastfeeding has beneficial effects on the neonates’ health.

Jean François Gauchat

Papers

Prototypic Long Pentraxin PTX3 Is Present in Breast Milk, Spreads in Tissues, and Protects Neonate Mice from Pseudomonas aeruginosa Lung Infection