The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens.
Pentraxins are soluble pattern recognition receptors with a dual role: protection against extracellular microbes and autoimmunity. The mechanisms by which they accomplish these tasks are not yet fully understood. Here we show that the prototypic long pentraxin PTX3 is specifically recruited at both sides of the phagocytic synapse between dendritic cells (DCs) and dying cells and remains stably bound to the apoptotic membranes (estimated half-time > 36 hours). Apoptotic cells per se influence the production of PTX3 by maturing DCs. When both microbial stimuli and dying cells are present, PTX3 behaves as a flexible adaptor of DC function, regulating the maturation program and the secretion of soluble factors. Moreover a key event associated with autoimmunity (ie, the cross-presentation of epitopes expressed by apoptotic cells to T cells) abates in the presence of PTX3, as evaluated using self, viral, and tumor-associated model antigens (vinculin, NS3, and MelanA/MART1). In contrast, PTX3 did not influence the presentation of exogenous soluble antigens, an event required for immunity against extracellular pathogens. These data suggest that PTX3 acts as a third-party agent between microbial stimuli and dying cells, contributing to limit tissue damage under inflammatory conditions and the activation of autoreactive T cells.
Baruah
Paramita
P
Cancer Immunotherapy & Gene Therapy Program, H San Raffaele Institute, Milan, Italy.
Propato
Antonella
A
Dumitriu
Ingrid E
IE
Rovere-Querini
Patrizia
P
Russo
Vincenzo
V
Fontana
Raffaella
R
Accapezzato
Daniele
D
Peri
Giuseppe
G
Mantovani
Alberto
A
Barnaba
Vincenzo
V
Manfredi
Angelo A
AA
D016475:3T3 Cells; D000818:Animals; D000914:Antibodies, Viral; D017951:Antigen Presentation; D000951:Antigens, Neoplasm; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens; D015551:Autoimmunity; D002097:C-Reactive Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D000683:Serum Amyloid P-Component / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014162:Transfection; D000099153:Pentraxins
D000914:Antibodies, Viral; D000951:Antigens, Neoplasm; D001324:Autoantigens; D002097:C-Reactive Protein; D000683:Serum Amyloid P-Component; D000099153:Pentraxins