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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}

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