<named-content content-type="genus-species">Staphylococcus aureus</named-content> Infects Osteoclasts and Replicates Intracellularly

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....

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Autores principales:	Jennifer L. Krauss, Philip M. Roper, Anna Ballard, Chien-Cheng Shih, James A. J. Fitzpatrick, James E. Cassat, Pei Ying Ng, Nathan J. Pavlos, Deborah J. Veis
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Staphylococcus aureus bone osteoclasts osteomyelitis RANKL intracellular bacteria Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/38ab3b65e90648ecafb217df2a168e19
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spelling	oai:doaj.org-article:38ab3b65e90648ecafb217df2a168e192021-11-15T15:59:41Z<named-content content-type="genus-species">Staphylococcus aureus</named-content> Infects Osteoclasts and Replicates Intracellularly10.1128/mBio.02447-192150-7511https://doaj.org/article/38ab3b65e90648ecafb217df2a168e192019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02447-19https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE 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.Jennifer L. KraussPhilip M. RoperAnna BallardChien-Cheng ShihJames A. J. FitzpatrickJames E. CassatPei Ying NgNathan J. PavlosDeborah J. VeisAmerican Society for MicrobiologyarticleStaphylococcus aureusboneosteoclastsosteomyelitisRANKLintracellular bacteriaMicrobiologyQR1-502ENmBio, Vol 10, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus aureus bone osteoclasts osteomyelitis RANKL intracellular bacteria Microbiology QR1-502
spellingShingle	Staphylococcus aureus bone osteoclasts osteomyelitis RANKL intracellular bacteria Microbiology QR1-502 Jennifer L. Krauss Philip M. Roper Anna Ballard Chien-Cheng Shih James A. J. Fitzpatrick James E. Cassat Pei Ying Ng Nathan J. Pavlos Deborah J. Veis <named-content content-type="genus-species">Staphylococcus aureus</named-content> Infects Osteoclasts and Replicates Intracellularly
description	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-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. IMPORTANCE 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.
format	article
author	Jennifer L. Krauss Philip M. Roper Anna Ballard Chien-Cheng Shih James A. J. Fitzpatrick James E. Cassat Pei Ying Ng Nathan J. Pavlos Deborah J. Veis
author_facet	Jennifer L. Krauss Philip M. Roper Anna Ballard Chien-Cheng Shih James A. J. Fitzpatrick James E. Cassat Pei Ying Ng Nathan J. Pavlos Deborah J. Veis
author_sort	Jennifer L. Krauss
title	<named-content content-type="genus-species">Staphylococcus aureus</named-content> Infects Osteoclasts and Replicates Intracellularly
title_short	<named-content content-type="genus-species">Staphylococcus aureus</named-content> Infects Osteoclasts and Replicates Intracellularly
title_full	<named-content content-type="genus-species">Staphylococcus aureus</named-content> Infects Osteoclasts and Replicates Intracellularly
title_fullStr	<named-content content-type="genus-species">Staphylococcus aureus</named-content> Infects Osteoclasts and Replicates Intracellularly
title_full_unstemmed	<named-content content-type="genus-species">Staphylococcus aureus</named-content> Infects Osteoclasts and Replicates Intracellularly
title_sort	<named-content content-type="genus-species">staphylococcus aureus</named-content> infects osteoclasts and replicates intracellularly
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/38ab3b65e90648ecafb217df2a168e19
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<named-content content-type="genus-species">Staphylococcus aureus</named-content> Infects Osteoclasts and Replicates Intracellularly

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