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Nature 420, 182-186 (14 November 2002) | doi:10.1038/nature01195; Received 26 July 2002; Accepted 8 October 2002

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

Cecilia Garlanda1,2, Emilio Hirsch2,3, Silvia Bozza4, Antonietta Salustri5, Marika De Acetis3, Rachele Nota1, Alessia Maccagno5, Federica Riva1, Barbara Bottazzi1, Giuseppe Peri1, Andrea Doni1, Luca Vago6, Marina Botto7, Rita De Santis8, Paolo Carminati8, Gregorio Siracusa5, Fiorella Altruda3, Annunciata Vecchi1, Luigina Romani4 & Alberto Mantovani1,10

  1. Department of Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, 20157 Milan, Italy
  2. Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy
  3. Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
  4. Department of Public Health and Cell Biology, Roma Tor Vergata University, Rome, Italy
  5. Institute of Pathology, University of Milan, Ospedale Luigi Sacco, Milan, Italy
  6. Rheumatology Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK
  7. SigmaTau SpA, Pomezia, Rome, Italy
  8. Centro IDET, Institute of General Pathology, University of Milan, Milan, Italy
  9. These authors contributed equally to this work

Correspondence to: Alberto Mantovani1,10 Correspondence and requests for materials should be addressed to A.M. (e-mail: Email: mantovani@marionegri.it).

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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.