Listeria monocytogenes induces IFNβ expression through an IFI16-, cGAS- and STING-dependent pathway

Kathrine Hansen1, Thaneas Prabakaran1, Anders Laustsen1

  • 1Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.

The EMBO Journal
|June 28, 2014
PubMed

Insights

In human myeloid cells, Listeria DNA, not cyclic-di-AMP, triggers Interferon β (IFNβ) production. This response is mediated by IFI16, cGAS, and STING, revealing a key pathway in Listeria infection immunity.

Area of Science:

  • Immunology
  • Microbiology
  • Cellular Biology

Background:

  • Listeria monocytogenes is a gram-positive bacterium that infects myeloid cells.
  • Interferon β (IFNβ) is crucial in Listeria disease pathogenesis.
  • The mechanism of IFNβ induction in human myeloid cells during Listeria infection is not fully understood.

Purpose of the Study:

  • To elucidate the mechanism of IFNβ expression in human myeloid cells upon Listeria monocytogenes infection.
  • To identify the bacterial molecules and host sensors involved in initiating the IFNβ response.

Main Methods:

  • Human macrophages were infected with Listeria monocytogenes.
  • Investigated the role of cyclic-di-AMP versus bacterial DNA in triggering the IFN response.
  • Utilized genetic and molecular techniques to assess the involvement of IFI16, cGAS, and STING pathways.

Main Results:

  • Listeria DNA, not cyclic-di-AMP, was identified as the primary stimulus for IFNβ production in human macrophages.
  • The IFN response was dependent on the DNA sensors IFI16 and cGAS.
  • The signaling adaptor molecule STING was essential for mediating the downstream signaling cascade.

Conclusions:

  • Bacterial DNA is a critical trigger for IFNβ expression in human myeloid cells during Listeria infection.
  • The IFI16-cGAS-STING pathway is essential for sensing Listeria DNA and activating the innate immune response.

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