The overlapping host responses to bacterial cyclic dinucleotides Journal Article
| Authors: | Abdul-Sater, A. A.; Grajkowski, A.; Erdjument-Bromage, H.; Plumlee, C.; Levi, A.; Schreiber, M. T.; Lee, C.; Shuman, H.; Beaucage, S. L.; Schindler, C. |
| Article Title: | The overlapping host responses to bacterial cyclic dinucleotides |
| 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. © 2011 Institut Pasteur. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; nonhuman; ultraviolet radiation; protein analysis; animal cell; inflammation; bacterial strain; cell fractionation; innate immunity; macrophage; beta interferon; dinucleotide; cross linking; legionella pneumophila; cyclic dinucleotides; cytokines and signal transduction; interferons (ifns); l. pneumophila; pamps; cyclic 3'5' diadenylate; cyclic 3'5' diguanylate |
| Journal Title: | Microbes and Infection |
| Volume: | 14 |
| Issue: | 2 |
| ISSN: | 1286-4579 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2012-02-01 |
| Start Page: | 188 |
| End Page: | 197 |
| Language: | English |
| DOI: | 10.1016/j.micinf.2011.09.002 |
| PROVIDER: | scopus |
| PUBMED: | 21933720 |
| PMCID: | PMC3518029 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2012" - "CODEN: MCINF" - "Source: Scopus" |
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