Cyclic di-AMP released from Staphylococcus aureus biofilm induces a macrophage type I interferon response

Casey M. Gries, Eric L. Bruger, Derek E. Moormeier, Tyler D. Scherr, Christopher M. Waters, Tammy L Kielian

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Staphylococcus aureus is a leading cause of community- and nosocomial-acquired infections, with a propensity for biofilm formation. S. aureus biofilms actively skew the host immune response toward an anti-inflammatory state; however, the biofilm effector molecules and the mechanism(s) of action responsible for this phenomenon remain to be fully defined. The essential bacterial second messenger cyclic diadenylate monophosphate (c-di-AMP) is an emerging pathogen-associated molecular pattern during intracellular bacterial infections, as c-di-AMP secretion into the infected host cytosol induces a robust type I interferon (IFN) response. Type I IFNs have the potential to exacerbate infectious outcomes by promoting anti-inflammatory effects; however, the type I IFN response to S. aureus biofilms is unknown. Additionally, while several intracellular proteins function as c-di- AMP receptors in S. aureus, it has yet to be determined if any extracellular role for c-di-AMP exists and its release during biofilm formation has not yet been demonstrated. This study examined the possibility that c-di-AMP released during S. aureus biofilm growth polarizes macrophages toward an anti-inflammatory phenotype via type I interferon signaling. DacA, the enzyme responsible for c-di-AMP synthesis in S. aureus, was highly expressed during biofilm growth, and 30 to 50% of total c-di-AMP produced from S. aureus biofilm was released extracellularly due to autolytic activity. S. aureus biofilm c-di-AMP release induced macrophage type I IFN expression via a STING-dependent pathway and promoted S. aureus intracellular survival in macrophages. These findings identify c-di-AMP as another mechanism for how S. aureus biofilms promote macrophage anti-inflammatory activity, which likely contributes to biofilm persistence.

Original languageEnglish (US)
Pages (from-to)3564-3574
Number of pages11
JournalInfection and immunity
Volume84
Issue number12
DOIs
StatePublished - Jan 1 2016

Fingerprint

Interferon Type I
Biofilms
Cyclic AMP
Staphylococcus aureus
Macrophages
Anti-Inflammatory Agents
Community-Acquired Infections
Community Hospital
Second Messenger Systems
Growth
Cross Infection
Bacterial Infections
Cytosol

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Cyclic di-AMP released from Staphylococcus aureus biofilm induces a macrophage type I interferon response. / Gries, Casey M.; Bruger, Eric L.; Moormeier, Derek E.; Scherr, Tyler D.; Waters, Christopher M.; Kielian, Tammy L.

In: Infection and immunity, Vol. 84, No. 12, 01.01.2016, p. 3564-3574.

Research output: Contribution to journalArticle

Gries, Casey M. ; Bruger, Eric L. ; Moormeier, Derek E. ; Scherr, Tyler D. ; Waters, Christopher M. ; Kielian, Tammy L. / Cyclic di-AMP released from Staphylococcus aureus biofilm induces a macrophage type I interferon response. In: Infection and immunity. 2016 ; Vol. 84, No. 12. pp. 3564-3574.
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