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

被引:548
|
作者
Garlanda, C
Hirsch, E
Bozza, S
Salustri, A
De Acetis, M
Nota, R
Maccagno, A
Riva, F
Bottazzi, B
Peri, G
Doni, A
Vago, L
Botto, M
De Santis, R
Carminati, P
Siracusa, G
Altruda, F
Vecchi, A
Romani, L
Mantovani, A
机构
[1] Mario Negri Inst Pharmacol Res, Dept Immunol & Cell Biol, I-20157 Milan, Italy
[2] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy
[3] Univ Perugia, Dept Expt Med & Biochem Sci, Microbiol Sect, I-06100 Perugia, Italy
[4] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Rome, Italy
[5] Univ Milan, Osped Luigi Sacco, Inst Pathol, Milan, Italy
[6] Imperial Coll Sch Med, Hammersmith Hosp, Div Med, Rheumatol Sect, London, England
[7] SigmaTau SpA, Rome, Italy
[8] Univ Milan, Inst Gen Pathol, Ctr IDET, Milan, Italy
关键词
D O I
10.1038/nature01195
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pentraxins are a superfamily of conserved proteins that are characterized by a cyclic multimeric structure(1). 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(2-4). Short pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components(2-5). 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(6). 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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页码:182 / 186
页数:5
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