$Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model$
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Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model

Biomechanical stability plays an important role in fracture healing, with unstable fixation being associated with healing disturbances. A lack of stability is also considered a risk factor for fracture-related infection (FRI), although confirmatory studies and an understanding of the underlying mech...

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Autores principales:	Marina Sabaté-Brescó, Corina M. Berset, Stephan Zeiter, Barbara Stanic, Keith Thompson, Mario Ziegler, R. Geoff Richards, Liam O'Mahony, T. Fintan Moriarty
Formato:	article
Lenguaje:	EN
Publicado:	The Company of Biologists 2021
Materias:	bone infection fracture-related infection s. epidermidis s. aureus implant stability interleukin-17a Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/00e517bf17264744889f08025ba0617c
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spelling	oai:doaj.org-article:00e517bf17264744889f08025ba0617c2021-11-28T16:01:02ZFracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model2046-639010.1242/bio.057315https://doaj.org/article/00e517bf17264744889f08025ba0617c2021-09-01T00:00:00Zhttp://bio.biologists.org/content/10/9/bio057315https://doaj.org/toc/2046-6390Biomechanical stability plays an important role in fracture healing, with unstable fixation being associated with healing disturbances. A lack of stability is also considered a risk factor for fracture-related infection (FRI), although confirmatory studies and an understanding of the underlying mechanisms are lacking. In the present study, we investigate whether biomechanical (in)stability can lead to altered immune responses in mice under sterile or experimentally inoculated conditions. In non-inoculated C57BL/6 mice, instability resulted in an early increase of inflammatory markers such as granulocyte-colony stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin (IL)-6 within the bone. When inoculated with Staphylococcus epidermidis, instability resulted in a further significant increase in G-CSF, IL-6 and KC in bone tissue. Staphylococcus aureus infection led to rapid osteolysis and instability in all animals and was not further studied. Gene expression measurements also showed significant upregulation in CCL2 and G-CSF in these mice. IL-17A was found to be upregulated in all S. epidermidis infected mice, with higher systemic IL-17A cell responses in mice that cleared the infection, which was found to be produced by CD4+ and γδ+ T cells in the bone marrow. IL-17A knock-out (KO) mice displayed a trend of delayed clearance of infection (P=0.22, Fisher’s exact test) and an increase in interferon (IFN)-γ production. Biomechanical instability leads to a more pronounced local inflammatory response, which is exaggerated by bacterial infection. This study provides insights into long-held beliefs that biomechanics are crucial not only for fracture healing, but also for control of infection.Marina Sabaté-BrescóCorina M. BersetStephan ZeiterBarbara StanicKeith ThompsonMario ZieglerR. Geoff RichardsLiam O'MahonyT. Fintan MoriartyThe Company of Biologistsarticlebone infectionfracture-related infections. epidermidiss. aureusimplant stabilityinterleukin-17aScienceQBiology (General)QH301-705.5ENBiology Open, Vol 10, Iss 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bone infection fracture-related infection s. epidermidis s. aureus implant stability interleukin-17a Science Q Biology (General) QH301-705.5
spellingShingle	bone infection fracture-related infection s. epidermidis s. aureus implant stability interleukin-17a Science Q Biology (General) QH301-705.5 Marina Sabaté-Brescó Corina M. Berset Stephan Zeiter Barbara Stanic Keith Thompson Mario Ziegler R. Geoff Richards Liam O'Mahony T. Fintan Moriarty Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model
description	Biomechanical stability plays an important role in fracture healing, with unstable fixation being associated with healing disturbances. A lack of stability is also considered a risk factor for fracture-related infection (FRI), although confirmatory studies and an understanding of the underlying mechanisms are lacking. In the present study, we investigate whether biomechanical (in)stability can lead to altered immune responses in mice under sterile or experimentally inoculated conditions. In non-inoculated C57BL/6 mice, instability resulted in an early increase of inflammatory markers such as granulocyte-colony stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin (IL)-6 within the bone. When inoculated with Staphylococcus epidermidis, instability resulted in a further significant increase in G-CSF, IL-6 and KC in bone tissue. Staphylococcus aureus infection led to rapid osteolysis and instability in all animals and was not further studied. Gene expression measurements also showed significant upregulation in CCL2 and G-CSF in these mice. IL-17A was found to be upregulated in all S. epidermidis infected mice, with higher systemic IL-17A cell responses in mice that cleared the infection, which was found to be produced by CD4+ and γδ+ T cells in the bone marrow. IL-17A knock-out (KO) mice displayed a trend of delayed clearance of infection (P=0.22, Fisher’s exact test) and an increase in interferon (IFN)-γ production. Biomechanical instability leads to a more pronounced local inflammatory response, which is exaggerated by bacterial infection. This study provides insights into long-held beliefs that biomechanics are crucial not only for fracture healing, but also for control of infection.
format	article
author	Marina Sabaté-Brescó Corina M. Berset Stephan Zeiter Barbara Stanic Keith Thompson Mario Ziegler R. Geoff Richards Liam O'Mahony T. Fintan Moriarty
author_facet	Marina Sabaté-Brescó Corina M. Berset Stephan Zeiter Barbara Stanic Keith Thompson Mario Ziegler R. Geoff Richards Liam O'Mahony T. Fintan Moriarty
author_sort	Marina Sabaté-Brescó
title	Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model
title_short	Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model
title_full	Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model
title_fullStr	Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model
title_full_unstemmed	Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model
title_sort	fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model
publisher	The Company of Biologists
publishDate	2021
url	https://doaj.org/article/00e517bf17264744889f08025ba0617c
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_version_	1718407811865509888

Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model

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