Staphylococcus aureus Infects Osteoclasts and Replicates Intracellularly
| Autor: | Nathan J. Pavlos, Deborah J. Veis, Jennifer L. Krauss, James A. J. Fitzpatrick, Anna Ballard, Chien-Cheng Shih, Pei Ying Ng, Philip M Roper, James E. Cassat |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases Male Staphylococcus aureus Osteoclasts Inflammation Biology medicine.disease_cause Microbiology Phagolysosome bone Bone remodeling Host-Microbe Biology 03 medical and health sciences Mice 0302 clinical medicine Immune system Gentamicin protection assay Bacterial Proteins Virology Phagosomes medicine Animals Cells Cultured 030304 developmental biology 0303 health sciences Osteoblasts intracellular bacteria Intracellular parasite Macrophages RANK Ligand RANKL osteomyelitis Cell Differentiation QR1-502 3. Good health 030104 developmental biology medicine.anatomical_structure biology.protein Female Bone marrow medicine.symptom Intracellular 030217 neurology & neurosurgery Research Article |
| Zdroj: | mBio mBio, Vol 10, Iss 5, p e02447-19 (2019) mBio, Vol 10, Iss 5 (2019) |
| ISSN: | 2150-7511 |
| Popis: | The inflammation of bone tissue is called osteomyelitis, and most cases are caused by an infection with the bacterium Staphylococcus aureus. To date, the bone-building cells, osteoblasts, have been implicated in the progression of these infections, but not much is known about how the bone-resorbing cells, osteoclasts, participate. In this study, we show that S. aureus can infect osteoclasts and proliferate inside these cells, whereas bone-residing macrophages, immune cells related to osteoclasts, destroy the bacteria. These findings elucidate a unique role for osteoclasts to harbor bacteria during infection, providing a possible mechanism by which bacteria could evade destruction by the immune system. 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-κB, 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|