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 language | English |
|---|---|
| Pages (from-to) | 182-186 |
| Number of pages | 5 |
| Journal | Nature |
| Volume | 420 |
| Issue number | 6912 |
| DOIs | |
| Publication status | Published - Nov 14 2002 |
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Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. / Garianda, Cecilia; Hirsch, Emilio; Bozza, Silvia; Salustri, Antonietta; De Acetis, Marika; Nota, Rachele; Maccagno, Alessia; Riva, Federica; Bottazzi, Barbara; Peri, Giuseppe; Doni, Andrea; Vago, Luca; Botto, Marina; De Santis, Rita; Carminati, Paolo; Siracusa, Gregorio; Altruda, Florella; Vecchi, Annunciata; Romani, Luigina; Mantovani, Alberto.
In: Nature, Vol. 420, No. 6912, 14.11.2002, p. 182-186.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response
AU - Garianda, Cecilia
AU - Hirsch, Emilio
AU - Bozza, Silvia
AU - Salustri, Antonietta
AU - De Acetis, Marika
AU - Nota, Rachele
AU - Maccagno, Alessia
AU - Riva, Federica
AU - Bottazzi, Barbara
AU - Peri, Giuseppe
AU - Doni, Andrea
AU - Vago, Luca
AU - Botto, Marina
AU - De Santis, Rita
AU - Carminati, Paolo
AU - Siracusa, Gregorio
AU - Altruda, Florella
AU - Vecchi, Annunciata
AU - Romani, Luigina
AU - Mantovani, Alberto
PY - 2002/11/14
Y1 - 2002/11/14
N2 - 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.
AB - 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.
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U2 - 10.1038/nature01195
DO - 10.1038/nature01195
M3 - Article
C2 - 12432394
AN - SCOPUS:18744372691
VL - 420
SP - 182
EP - 186
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6912
ER -