TBK1 protects vacuolar integrity during intracellular bacterial infection

Andrea L. Radtke, Laura M. Delbridge, Siddharth Balachandran, Glen N Barber, Mary X D O'Riordan

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

TANK-binding kinase-1 (TBK1) is an integral component of Type I interferon induction by microbial infection. The importance of TBK1 and Type I interferon in antiviral immunity is well established, but the function of TBK1 in bacterial infection is unclear. Upon infection of murine embryonic fibroblasts with Salmonella enterica serovar Typhimurium (Salmonella), more extensive bacterial proliferation was observed in tbk1-/- than tbk1+/+ cells. TBK1 kinase activity was required for restriction of bacterial infection, but interferon regulatory factor-3 or Type I interferon did not contribute to this TBK1-dependent function. In tbk1-/-cells, Salmonella, enteropathogenic Escherichia coli, and Streptococcus pyogenes escaped from vacuoles into the cytosol where increased replication occurred, which suggests that TBK1 regulates the integrity of pathogen-containing vacuoles. Knockdown of tbk1 in macrophages and epithelial cells also resulted in increased bacterial localization in the cytosol, indicating that the role of TBK1 in maintaining vacuolar integrity is relevant in different cell types. Taken together, these data demonstrate a requirement for TBK1 in control of bacterial infection distinct from its established role in antiviral immunity.

Original languageEnglish
JournalPLoS Pathogens
Volume3
Issue number3
DOIs
StatePublished - Mar 1 2007

Fingerprint

Bacterial Infections
Phosphotransferases
Interferon Type I
Vacuoles
Cytosol
Antiviral Agents
Immunity
Interferon Regulatory Factor-3
Enteropathogenic Escherichia coli
Salmonella enterica
Streptococcus pyogenes
Salmonella typhimurium
Infection
Salmonella
Fibroblasts
Epithelial Cells
Macrophages

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

TBK1 protects vacuolar integrity during intracellular bacterial infection. / Radtke, Andrea L.; Delbridge, Laura M.; Balachandran, Siddharth; Barber, Glen N; O'Riordan, Mary X D.

In: PLoS Pathogens, Vol. 3, No. 3, 01.03.2007.

Research output: Contribution to journalArticle

Radtke, Andrea L. ; Delbridge, Laura M. ; Balachandran, Siddharth ; Barber, Glen N ; O'Riordan, Mary X D. / TBK1 protects vacuolar integrity during intracellular bacterial infection. In: PLoS Pathogens. 2007 ; Vol. 3, No. 3.
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