Staphylococcus aureus infects osteoclasts and replicates intracellularly

Jennifer L. Krauss, Philip M. Roper, Anna Ballard, Chien Cheng Shih, James A.J. Fitzpatrick, James E. Cassat, Ng Pei Ying, Nathan J. Pavlos, Deborah J. Veisa

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Osteomyelitis (OM), or inflammation of bone tissue, occurs most frequently as a result of bacterial infection and severely perturbs bone structure. OM is predominantly caused by Staphylococcus aureus, and even with proper treatment, OM has a high rate of recurrence and chronicity. While S. aureus has been shown to infect osteoblasts, it remains unclear whether osteoclasts (OCs) are also a target of intracellular infection. Here, we demonstrate the ability of S. aureus to intracellularly infect and divide within OCs. OCs were differentiated from bone marrow macrophages (BMMs) by exposure to receptor activator of nuclear factor kappa-B ligand (RANKL). By utilizing an intracellular survival assay and flow cytometry, we found that at 18 h postinfection the intracellular burden of S. aureus increased dramatically in cells with at least 2 days of RANKL exposure, while the bacterial burden decreased in BMMs. To further explore the signals downstream of RANKL, we manipulated factors controlling OC differentiation, NFATc1 and alternative NF-B, and found that intracellular bacterial growth correlates with NFATc1 levels in RANKL-treated cells. Confocal and time-lapse microscopy in mature OCs showed a range of intracellular infection that correlated inversely with S. aureus-phagolysosome colocalization. The propensity of OCs to become infected, paired with their diminished bactericidal capacity compared to BMMs, could promote OM progression by allowing S. aureus to evade initial immune regulation and proliferate at the periphery of lesions where OCs are most abundant.

Original languageEnglish
Article numbere02447-19
JournalmBio
Volume10
Issue number5
DOIs
StatePublished - 2019

Keywords

  • Bone
  • Intracellular bacteria
  • Osteoclasts
  • Osteomyelitis
  • RANKL
  • Staphylococcus aureus

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