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

Nature volume 420, pages 182–186 (2002)Cite this article

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.

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Figure 1: Interaction of Ptx3 with selected pathogens.
Figure 2: Induction of Ptx3 by A. fumigatus in vitro and in vivo and its role in promoting recognition of conidia.
Figure 3: Selective susceptibility of Ptx3-/- mice to A. fumigatus.

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Acknowledgements

This work was supported by Istituto Superiore di Sanità, Ministero Istruzione, Università e Ricerca (MIUR), Consiglio Nazionale della Richerche (CNR), and by the European Commission. We acknowledge the contribution of the Italian Association for Cancer Research. We thank C. Scotton for critical reading of the manuscript.

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Author notes

  1. Cecilia Garlanda and Emilio Hirsch: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, 20157, Milan, Italy

    Cecilia Garlanda, Rachele Nota, Federica Riva, Barbara Bottazzi, Giuseppe Peri, Andrea Doni, Annunciata Vecchi & Alberto Mantovani

  2. Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy

    Emilio Hirsch, Marika De Acetis & Fiorella Altruda

  3. Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy

    Silvia Bozza & Luigina Romani

  4. Department of Public Health and Cell Biology, Roma Tor Vergata University, Rome, Italy

    Antonietta Salustri, Alessia Maccagno & Gregorio Siracusa

  5. Institute of Pathology, University of Milan, Ospedale Luigi Sacco, Milan, Italy

    Luca Vago

  6. Rheumatology Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK

    Marina Botto

  7. SigmaTau SpA, Pomezia, Rome, Italy

    Rita De Santis & Paolo Carminati

  8. Centro IDET, Institute of General Pathology, University of Milan, Milan, Italy

    Alberto Mantovani

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Corresponding author

Correspondence to Alberto Mantovani.

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Competing interests

R.D.S. and P.C. are employees of Sigma Tau, interested in exploiting the therapeutic potential of Ptx3. C.G., B.B., G.P. and A.M. are inventors in patent applications concerning Ptx3.

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Garlanda, C., Hirsch, E., Bozza, S. et al. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420, 182–186 (2002). https://doi.org/10.1038/nature01195

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