期刊
MICROBES AND INFECTION
卷 14, 期 2, 页码 188-197出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.micinf.2011.09.002
关键词
L. pneumophila; Cyclic dinucleotides; PAMPs; Interferons (ifns); Cytokines and signal transduction
资金
- NIH [AI096088, AI058211, AI23549]
Macrophages respond to infection with Legionella pneumophila by the induction of inflammatory mediators, including type I Interferons (IFN-Is). To explore whether the bacterial second messenger cyclic 3'-5' diguanylate (c-diGMP) activates some of these mediators, macrophages were infected with L. pneumophila strains in which the levels of bacterial c-diGMP had been altered. Intriguingly, there was a positive correlation between c-diGMP levels and IFN-I expression. Subsequent studies with synthetic derivatives of c-diGMP, and newly described cyclic 3'-5' diadenylate (c-diAMP), determined that these molecules activate overlapping inflammatory responses in human and murine macrophages. Moreover, UV crosslinking studies determined that both dinucleotides physically associate with a shared set of host proteins. Fractionation of macrophage extracts on a biotin-c-diGMP affinity matrix led to the identification of a set of candidate host binding proteins. These studies suggest that mammalian macrophages can sense and mount a specific inflammatory response to bacterial dinucleotides. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
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