Abstract:
: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.
journal_name
Microbes Infectjournal_title
Microbes and infectionauthors
Abdul-Sater AA,Grajkowski A,Erdjument-Bromage H,Plumlee C,Levi A,Schreiber MT,Lee C,Shuman H,Beaucage SL,Schindler Cdoi
10.1016/j.micinf.2011.09.002subject
Has Abstractpub_date
2012-02-01 00:00:00pages
188-97issue
2eissn
1286-4579issn
1769-714Xpii
S1286-4579(11)00234-6journal_volume
14pub_type
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