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The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection
被引:405
作者:
Zamboni, DS
Kobayashi, KS
Kohlsdorf, T
Ogura, Y
Long, EM
Vance, RE
Kuida, K
Mariathasan, S
Dixit, VM
Flavell, RA
Dietrich, WF
Roy, CR
[1
]
机构:
[1] Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA
[4] Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06510 USA
[5] Yale Univ, Sch Med, Dept Ecol & Evolutionary Biol, New Haven, CT 06510 USA
[6] Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02115 USA
[7] Vertex Pharmaceut, Cambridge, MA 02139 USA
[8] Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA
关键词:
D O I:
10.1038/ni1305
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Baculovirus inhibitor of apoptosis repeat-containing 1 (Birc1) proteins have homology to several germline-encoded receptors of the innate immune system. However, their function in immune surveillance is not clear. Here we describe a Birc1e-dependent signaling pathway that restricted replication of the intracellular pathogen Legionella pneumophila in mouse macrophages. Translocation of bacterial products into host-cell cytosol was essential for Birc1e-mediated control of bacterial replication. Caspase-1 was required for Birc1e-dependent antibacterial responses ex vivo in macrophages and in a mouse model of Legionnaires' disease. The interleukin 1 beta converting enzyme-protease-activating factor was necessary for L. pneumophila growth restriction, but interleukin 1 beta was not required. These results establish Birc1e as a nucleotide-binding oligomerization-leucine-rich repeat protein involved in the detection and control of intracellular L. pneumophila.
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页码:318 / 325
页数:8
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