• 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.
• Department of Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, 20157 Milan, Italy.
• Nature. 2002 Nov 14;420(6912):182-6.

AbstractPentraxins are a superfamily of conserved proteins that are characterized by a cyclic multimeric structure. 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 mediators. Short pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components. 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.

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