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

Cecilia Garlanda, 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, Fiorella Altruda, Annunciata Vecchi, Luigina Romani and Alberto Mantovani ()
Additional contact information
Cecilia Garlanda: Mario Negri Institute for Pharmacological Research
Emilio Hirsch: University of Turin
Silvia Bozza: University of Perugia
Antonietta Salustri: Roma Tor Vergata University
Marika De Acetis: University of Turin
Rachele Nota: Mario Negri Institute for Pharmacological Research
Alessia Maccagno: Roma Tor Vergata University
Federica Riva: Mario Negri Institute for Pharmacological Research
Barbara Bottazzi: Mario Negri Institute for Pharmacological Research
Giuseppe Peri: Mario Negri Institute for Pharmacological Research
Andrea Doni: Mario Negri Institute for Pharmacological Research
Luca Vago: Institute of Pathology, University of Milan, Ospedale Luigi Sacco
Marina Botto: Rheumatology Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital
Rita De Santis: SigmaTau SpA
Paolo Carminati: SigmaTau SpA
Gregorio Siracusa: Roma Tor Vergata University
Fiorella Altruda: University of Turin
Annunciata Vecchi: Mario Negri Institute for Pharmacological Research
Luigina Romani: University of Perugia
Alberto Mantovani: Mario Negri Institute for Pharmacological Research

Nature, 2002, vol. 420, issue 6912, 182-186

Abstract: 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 mediators2,3,4. Short pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components2,3,4,5. 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 ability6. 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.

Date: 2002
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DOI: 10.1038/nature01195

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