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...

Descripción completa

Guardado en:
Detalles Bibliográficos
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:
Q
Acceso en línea:https://doaj.org/article/00e517bf17264744889f08025ba0617c
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:00e517bf17264744889f08025ba0617c
record_format dspace
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
work_keys_str_mv AT marinasabatebresco fracturebiomechanicsinfluencelocalandsystemicimmuneresponsesinamurinefracturerelatedinfectionmodel
AT corinamberset fracturebiomechanicsinfluencelocalandsystemicimmuneresponsesinamurinefracturerelatedinfectionmodel
AT stephanzeiter fracturebiomechanicsinfluencelocalandsystemicimmuneresponsesinamurinefracturerelatedinfectionmodel
AT barbarastanic fracturebiomechanicsinfluencelocalandsystemicimmuneresponsesinamurinefracturerelatedinfectionmodel
AT keiththompson fracturebiomechanicsinfluencelocalandsystemicimmuneresponsesinamurinefracturerelatedinfectionmodel
AT marioziegler fracturebiomechanicsinfluencelocalandsystemicimmuneresponsesinamurinefracturerelatedinfectionmodel
AT rgeoffrichards fracturebiomechanicsinfluencelocalandsystemicimmuneresponsesinamurinefracturerelatedinfectionmodel
AT liamomahony fracturebiomechanicsinfluencelocalandsystemicimmuneresponsesinamurinefracturerelatedinfectionmodel
AT tfintanmoriarty fracturebiomechanicsinfluencelocalandsystemicimmuneresponsesinamurinefracturerelatedinfectionmodel
_version_ 1718407811865509888