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Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms

Chronic staphylococcal osteomyelitis can persist for long time periods causing bone destruction. The ability of Staphylococcus aureus to develop chronic infections is linked to its capacity to invade and replicate within osteoblasts and osteocytes and to switch to a dormant phenotype called small co...

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Autores principales: Garcia-Moreno, Marina, Jordan, Paul M., Günther, Kerstin, Dau, Therese, Fritzsch, Christian, Vermes, Monika, Schoppa, Astrid, Ignatius, Anita, Wildemann, Britt, Werz, Oliver, Löffler, Bettina, Tuchscherr, Lorena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355688/
https://www.ncbi.nlm.nih.gov/pubmed/35935196
http://dx.doi.org/10.3389/fmicb.2022.937466
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author Garcia-Moreno, Marina
Jordan, Paul M.
Günther, Kerstin
Dau, Therese
Fritzsch, Christian
Vermes, Monika
Schoppa, Astrid
Ignatius, Anita
Wildemann, Britt
Werz, Oliver
Löffler, Bettina
Tuchscherr, Lorena
author_facet Garcia-Moreno, Marina
Jordan, Paul M.
Günther, Kerstin
Dau, Therese
Fritzsch, Christian
Vermes, Monika
Schoppa, Astrid
Ignatius, Anita
Wildemann, Britt
Werz, Oliver
Löffler, Bettina
Tuchscherr, Lorena
author_sort Garcia-Moreno, Marina
collection PubMed
description Chronic staphylococcal osteomyelitis can persist for long time periods causing bone destruction. The ability of Staphylococcus aureus to develop chronic infections is linked to its capacity to invade and replicate within osteoblasts and osteocytes and to switch to a dormant phenotype called small colony variants. Recently, osteocytes were described as a main reservoir for this pathogen in bone tissue. However, the mechanisms involved in the persistence of S. aureus within these cells are still unknown. Here, we investigated the interaction between S. aureus and osteoblasts or osteocytes during infection. While osteoblasts are able to induce a strong antimicrobial response and eliminate intracellular S. aureus, osteocytes trigger signals to recruit immune cells and enhance inflammation but fail an efficient antimicrobial activity to clear the bacterial infection. Moreover, we found that extracellular signals from osteocytes enhance intracellular bacterial clearance by osteoblasts. Even though both cell types express Toll-like receptor (TLR) 2, the main TLR responsible for S. aureus detection, only osteoblasts were able to increase TLR2 expression after infection. Additionally, proteomic analysis indicates that reduced intracellular bacterial killing activity in osteocytes is related to low antimicrobial peptide expression. Nevertheless, high levels of lipid mediators and cytokines were secreted by osteocytes, suggesting that they can contribute to inflammation. Taken together, our results demonstrate that osteocytes contribute to severe inflammation observed in osteomyelitis and represent the main niche for S. aureus persistence due to their poor capacity for intracellular antimicrobial response.
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spelling pubmed-93556882022-08-06 Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms Garcia-Moreno, Marina Jordan, Paul M. Günther, Kerstin Dau, Therese Fritzsch, Christian Vermes, Monika Schoppa, Astrid Ignatius, Anita Wildemann, Britt Werz, Oliver Löffler, Bettina Tuchscherr, Lorena Front Microbiol Microbiology Chronic staphylococcal osteomyelitis can persist for long time periods causing bone destruction. The ability of Staphylococcus aureus to develop chronic infections is linked to its capacity to invade and replicate within osteoblasts and osteocytes and to switch to a dormant phenotype called small colony variants. Recently, osteocytes were described as a main reservoir for this pathogen in bone tissue. However, the mechanisms involved in the persistence of S. aureus within these cells are still unknown. Here, we investigated the interaction between S. aureus and osteoblasts or osteocytes during infection. While osteoblasts are able to induce a strong antimicrobial response and eliminate intracellular S. aureus, osteocytes trigger signals to recruit immune cells and enhance inflammation but fail an efficient antimicrobial activity to clear the bacterial infection. Moreover, we found that extracellular signals from osteocytes enhance intracellular bacterial clearance by osteoblasts. Even though both cell types express Toll-like receptor (TLR) 2, the main TLR responsible for S. aureus detection, only osteoblasts were able to increase TLR2 expression after infection. Additionally, proteomic analysis indicates that reduced intracellular bacterial killing activity in osteocytes is related to low antimicrobial peptide expression. Nevertheless, high levels of lipid mediators and cytokines were secreted by osteocytes, suggesting that they can contribute to inflammation. Taken together, our results demonstrate that osteocytes contribute to severe inflammation observed in osteomyelitis and represent the main niche for S. aureus persistence due to their poor capacity for intracellular antimicrobial response. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9355688/ /pubmed/35935196 http://dx.doi.org/10.3389/fmicb.2022.937466 Text en Copyright © 2022 Garcia-Moreno, Jordan, Günther, Dau, Fritzsch, Vermes, Schoppa, Ignatius, Wildemann, Werz, Löffler and Tuchscherr. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Garcia-Moreno, Marina
Jordan, Paul M.
Günther, Kerstin
Dau, Therese
Fritzsch, Christian
Vermes, Monika
Schoppa, Astrid
Ignatius, Anita
Wildemann, Britt
Werz, Oliver
Löffler, Bettina
Tuchscherr, Lorena
Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms
title Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms
title_full Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms
title_fullStr Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms
title_full_unstemmed Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms
title_short Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms
title_sort osteocytes serve as a reservoir for intracellular persisting staphylococcus aureus due to the lack of defense mechanisms
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355688/
https://www.ncbi.nlm.nih.gov/pubmed/35935196
http://dx.doi.org/10.3389/fmicb.2022.937466
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