Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response

Cecilia Garianda, Emilio Hirsch, Silvia Bozza, Antonietta Salustri, Marika De Acetis, Rachele Nota, Alessia Maccagno, Federica Riva, Barbara Bottazzi, Giuseppe Peri, Andrea Doni, Luca Vago, Marina Botto, Rita De Santis, Paolo Carminati, Gregorio Siracusa, Florella Altruda, Annunciata Vecchi, Luigina Romani, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

Pentraxins are a superfamily of conserved proteins that are characterized by a cyclic multimeric structure1. The classical short pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP), are acute-phase proteins produced in the liver in response to inflammatory mediators2-4. Short pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components2-5. In contrast, long pentraxins have an unrelated, long amino-terminal domain coupled to the carboxy-terminal pentraxin domain, and differ, with respect to short pentraxins, in their gene organization, chromosomal localization, cellular source, and in their stimuli-inducing and ligand-recognition ability. To investigate the in vivo function of the long pentraxin PTX3, we generated mice deficient in Ptx3 by homologous recombination. Ptx3-null mice were susceptible to invasive pulmonary aspergillosis. Ptx3 binds selected microbial agents, including conidia of Aspergillus fumigatus, and we found that susceptibility of Ptx3-null mice was associated with defective recognition of conidia by alveolar macrophages and dendritic cells, as well as inappropriate induction of an adaptive type 2 response. Thus, the long pentraxin Ptx3 is a secreted pattern-recognition receptor that has a non-redundant role in resistance to selected microbial agents, in particular to the opportunistic fungal pathogen Aspergillus fumigatus.

Original languageEnglish
Pages (from-to)182-186
Number of pages5
JournalNature
Volume420
Issue number6912
DOIs
Publication statusPublished - Nov 14 2002

ASJC Scopus subject areas

  • General

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