Identification of host cytosolic sensors and bacterial factors regulating the type I interferon response to Legionella pneumophila

PLoS Pathog. 2009 Nov;5(11):e1000665. doi: 10.1371/journal.ppat.1000665. Epub 2009 Nov 20.


Legionella pneumophila is a gram-negative bacterial pathogen that replicates in host macrophages and causes a severe pneumonia called Legionnaires' Disease. The innate immune response to L. pneumophila remains poorly understood. Here we focused on identifying host and bacterial factors involved in the production of type I interferons (IFN) in response to L. pneumophila. It was previously suggested that the delivery of L. pneumophila DNA to the host cell cytosol is the primary signal that induces the type I IFN response. However, our data are not easily reconciled with this model. We provide genetic evidence that two RNA-sensing proteins, RIG-I and MDA5, participate in the IFN response to L. pneumophila. Importantly, these sensors do not seem to be required for the IFN response to L. pneumophila DNA, whereas we found that RIG-I was required for the response to L. pneumophila RNA. Thus, we hypothesize that bacterial RNA, or perhaps an induced host RNA, is the primary stimulus inducing the IFN response to L. pneumophila. Our study also identified a secreted effector protein, SdhA, as a key suppressor of the IFN response to L. pneumophila. Although viral suppressors of cytosolic RNA-sensing pathways have been previously identified, analogous bacterial factors have not been described. Thus, our results provide new insights into the molecular mechanisms by which an intracellular bacterial pathogen activates and also represses innate immune responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cells, Cultured
  • Cytosol / metabolism*
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Disease Models, Animal
  • Host-Pathogen Interactions / physiology*
  • Immunity, Innate / physiology
  • Interferon Type I / metabolism*
  • Interferon-Induced Helicase, IFIH1
  • Legionella pneumophila / pathogenicity*
  • Legionnaires' Disease / metabolism*
  • Legionnaires' Disease / physiopathology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction / physiology


  • Adaptor Proteins, Signal Transducing
  • IPS-1 protein, mouse
  • Interferon Type I
  • Ddx58 protein, mouse
  • Ifih1 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1