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

Paramita Baruah, Antonella Propato, Ingrid E. Dumitriu, Patrizia Rovere-Querini, Vincenzo Russo, Raffaella Fontana, Daniele Accapezzato, Giuseppe Peri, Alberto Mantovani, Vincenzo Barnaba, Angelo A. Manfredi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)151-158
Number of pages8
JournalBlood
Volume107
Issue number1
DOIs
Publication statusPublished - Jan 1 2006

ASJC Scopus subject areas

  • Hematology

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