c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response.
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.
Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA.
Joshua J
JJ
Woodward
Anthony T
AT
Iavarone
Daniel A
DA
Portnoy
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D003600:Cytosol / Q000276:immunology / Q000382:microbiology; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D005260:Female; D005798:Genes, Bacterial; D007113:Immunity, Innate; D016899:Interferon-beta / Q000378:metabolism*; D008024:Ligands; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D013058:Mass Spectrometry; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D009876:Operon; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D015226:Dinucleoside Phosphates; D008024:Ligands; D026901:Membrane Transport Proteins; C528998:cyclic diadenosine phosphate; D016899:Interferon-beta; D019761:Phosphorus-Oxygen Lyases