Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 328 (5986): 1703-1705

Copyright © 2010 by the American Association for the Advancement of Science

c-di-AMP Secreted by Intracellular Listeria monocytogenes Activates a Host Type I Interferon Response

Joshua J. Woodward,1 Anthony T. Iavarone,2 Daniel A. Portnoy1,3,*

Abstract: Intracellular bacterial pathogens, such as Listeria monocytogenes, are detected in the cytosol of host immune cells. Induction of this host response is often dependent on microbial secretion systems and, in L. monocytogenes, is dependent on multidrug efflux pumps (MDRs). Using L. monocytogenes mutants that overexpressed MDRs, we identified cyclic diadenosine monophosphate (c-di-AMP) as a secreted molecule able to trigger the cytosolic host response. Overexpression of the di-adenylate cyclase, dacA (lmo2120), resulted in elevated levels of the host response during infection. c-di-AMP thus represents a putative bacterial secondary signaling molecule that triggers a cytosolic pathway of innate immunity and is predicted to be present in a wide variety of bacteria and archea.

1 Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA.
2 QB3/Chemistry Mass Spectrometry Facility, University of California, Berkeley, CA 94720, USA.
3 School of Public Health, University of California, Berkeley, CA 94720, USA.

* To whom correspondence should be addressed. E-mail: portnoy{at}berkeley.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Systematic identification of conserved bacterial c-di-AMP receptor proteins.
R. M. Corrigan, I. Campeotto, T. Jeganathan, K. G. Roelofs, V. T. Lee, and A. Grundling (2013)
PNAS 110, 9084-9089
   Abstract »    Full Text »    PDF »
Cyclic di-AMP Is Critical for Listeria monocytogenes Growth, Cell Wall Homeostasis, and Establishment of Infection.
C. E. Witte, A. T. Whiteley, T. P. Burke, J.-D. Sauer, D. A. Portnoy, and J. J. Woodward (2013)
mBio 4, e00282-13
   Abstract »    Full Text »    PDF »
STING-Dependent Recognition of Cyclic di-AMP Mediates Type I Interferon Responses during Chlamydia trachomatis Infection.
J. R. Barker, B. J. Koestler, V. K. Carpenter, D. L. Burdette, C. M. Waters, R. E. Vance, and R. H. Valdivia (2013)
mBio 4, e00018-13
   Abstract »    Full Text »    PDF »
STING/MPYS Mediates Host Defense against Listeria monocytogenes Infection by Regulating Ly6Chi Monocyte Migration.
L. Jin, A. Getahun, H. M. Knowles, J. Mogan, L. J. Akerlund, T. A. Packard, A.-L. Perraud, and J. C. Cambier (2013)
J. Immunol. 190, 2835-2843
   Abstract »    Full Text »    PDF »
Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger.
U. Romling, M. Y. Galperin, and M. Gomelsky (2013)
Microbiol. Mol. Biol. Rev. 77, 1-52
   Abstract »    Full Text »    PDF »
Molecular Basis of DNA Recognition in the Immune System.
M. K. Atianand and K. A. Fitzgerald (2013)
J. Immunol. 190, 1911-1918
   Abstract »    Full Text »    PDF »
Sensing the Dark Side of DNA.
L. A. J. O'Neill (2013)
Science 339, 763-764
   Abstract »    Full Text »    PDF »
Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA.
J. Wu, L. Sun, X. Chen, F. Du, H. Shi, C. Chen, and Z. J. Chen (2013)
Science 339, 826-830
   Abstract »    Full Text »    PDF »
DarR, a TetR-like Transcriptional Factor, Is a Cyclic Di-AMP-responsive Repressor in Mycobacterium smegmatis.
L. Zhang, W. Li, and Z.-G. He (2013)
J. Biol. Chem. 288, 3085-3096
   Abstract »    Full Text »    PDF »
Cyclic Di-AMP Homeostasis in Bacillus subtilis: BOTH LACK AND HIGH LEVEL ACCUMULATION OF THE NUCLEOTIDE ARE DETRIMENTAL FOR CELL GROWTH.
F. M. P. Mehne, K. Gunka, H. Eilers, C. Herzberg, V. Kaever, and J. Stulke (2013)
J. Biol. Chem. 288, 2004-2017
   Abstract »    Full Text »    PDF »
IRF3 contributes to sepsis pathogenesis in the mouse cecal ligation and puncture model.
W. E. Walker, A. T. Bozzi, and D. R. Goldstein (2012)
J. Leukoc. Biol. 92, 1261-1268
   Abstract »    Full Text »    PDF »
A {sigma}D-dependent antisense transcript modulates expression of the cyclic-di-AMP hydrolase GdpP in Bacillus subtilis.
Y. Luo and J. D. Helmann (2012)
Microbiology 158, 2732-2741
   Abstract »    Full Text »    PDF »
Listeria monocytogenes Strain-Specific Impairment of the TetR Regulator Underlies the Drastic Increase in Cyclic di-AMP Secretion and Beta Interferon-Inducing Ability.
T. Yamamoto, H. Hara, K. Tsuchiya, S. Sakai, R. Fang, M. Matsuura, T. Nomura, F. Sato, M. Mitsuyama, and I. Kawamura (2012)
Infect. Immun. 80, 2323-2332
   Abstract »    Full Text »    PDF »
Hyperinduction of Host Beta Interferon by a Listeria monocytogenes Strain Naturally Overexpressing the Multidrug Efflux Pump MdrT.
K. T. Schwartz, J. D. Carleton, S. J. Quillin, S. D. Rollins, D. A. Portnoy, and J. H. Leber (2012)
Infect. Immun. 80, 1537-1545
   Abstract »    Full Text »    PDF »
Genome-wide transcriptional profiling of the cell envelope stress response and the role of LisRK and CesRK in Listeria monocytogenes.
P. K. Nielsen, A. Z. Andersen, M. Mols, S. van der Veen, T. Abee, and B. H. Kallipolitis (2012)
Microbiology 158, 963-974
   Abstract »    Full Text »    PDF »
Streptococcus pneumoniae Stimulates a STING- and IFN Regulatory Factor 3-Dependent Type I IFN Production in Macrophages, which Regulates RANTES Production in Macrophages, Cocultured Alveolar Epithelial Cells, and Mouse Lungs.
U. Koppe, K. Hogner, J.-M. Doehn, H. C. Muller, M. Witzenrath, B. Gutbier, S. Bauer, T. Pribyl, S. Hammerschmidt, J. Lohmeyer, et al. (2012)
J. Immunol. 188, 811-817
   Abstract »    Full Text »    PDF »
Illuminating the landscape of host-pathogen interactions with the bacterium Listeria monocytogenes.
P. Cossart (2011)
PNAS 108, 19484-19491
   Abstract »    Full Text »    PDF »
Mutations of the Listeria monocytogenes Peptidoglycan N-Deacetylase and O-Acetylase Result in Enhanced Lysozyme Sensitivity, Bacteriolysis, and Hyperinduction of Innate Immune Pathways.
C. S. Rae, A. Geissler, P. C. Adamson, and D. A. Portnoy (2011)
Infect. Immun. 79, 3596-3606
   Abstract »    Full Text »    PDF »
MPYS Is Required for IFN Response Factor 3 Activation and Type I IFN Production in the Response of Cultured Phagocytes to Bacterial Second Messengers Cyclic-di-AMP and Cyclic-di-GMP.
L. Jin, K. K. Hill, H. Filak, J. Mogan, H. Knowles, B. Zhang, A.-L. Perraud, J. C. Cambier, and L. L. Lenz (2011)
J. Immunol. 187, 2595-2601
   Abstract »    Full Text »    PDF »
Listeria monocytogenes Infection Induces Prosurvival Metabolic Signaling in Macrophages.
T. Zou, O. Garifulin, R. Berland, and V. L. Boyartchuk (2011)
Infect. Immun. 79, 1526-1535
   Abstract »    Full Text »    PDF »
The N-Ethyl-N-Nitrosourea-Induced Goldenticket Mouse Mutant Reveals an Essential Function of Sting in the In Vivo Interferon Response to Listeria monocytogenes and Cyclic Dinucleotides.
J.-D. Sauer, K. Sotelo-Troha, J. von Moltke, K. M. Monroe, C. S. Rae, S. W. Brubaker, M. Hyodo, Y. Hayakawa, J. J. Woodward, D. A. Portnoy, et al. (2011)
Infect. Immun. 79, 688-694
   Abstract »    Full Text »    PDF »
Conidia but Not Yeast Cells of the Fungal Pathogen Histoplasma capsulatum Trigger a Type I Interferon Innate Immune Response in Murine Macrophages.
D. O. Inglis, C. A. Berkes, D. R. Hocking Murray, and A. Sil (2010)
Infect. Immun. 78, 3871-3882
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882