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Blood, 1 January 2006, Vol. 107, No. 1, pp. 151-158.
Prepublished online as a Blood First Edition Paper on September 15, 2005; DOI 10.1182/blood-2005-03-1112.
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Submitted March 18, 2005
Accepted August 25, 2005
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, and Angelo A Manfredi*
Cancer Immunotherapy & Gene Therapy Program, Clinical Immunology Unit, H San Raffaele Scientific Institute, Milano, Italy
Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna, Universita degli Studi di Roma La Sapienza, Rome, Italy
Cancer Gene Therapy Unit, H San Raffaele Scientific Institute, Milano, Italy
Mario Negri Institute for Pharmacological Research, Milan, Italy; Istituto Clinico Humanitas, Rozzano, Italy
Mario Negri Institute for Pharmacological Research, Milan, Italy; Istituto Clinico Humanitas, Rozzano, Italy; Centro di Eccellenza per l'Innovazione Diagnostica e Terapeutica (IDET), Institute of General Pathology, University of Milan, Milan, Italy
Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna, Universita degli Studi di Roma La Sapienza, Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Universita degli Studi di Roma La Sapienza, Rome, Italy
Cancer Immunotherapy & Gene Therapy Program, Clinical Immunology Unit, H San Raffaele Scientific Institute, Milano, Italy; Vita-Salute San Raffaele University, Milano, Italy
* Corresponding author; email: manfredi.angelo{at}hsr.it.
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, i.e. 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.
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