Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6135989 | Microbes and Infection | 2012 | 10 Pages |
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 3â²-5â² 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 3â²-5â² 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.
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Authors
Ali A. Abdul-Sater, Andrzej Grajkowski, Hediye Erdjument-Bromage, Courtney Plumlee, Assaf Levi, Michael T. Schreiber, Carolyn Lee, Howard Shuman, Serge L. Beaucage, Christian Schindler,