Cargando…

Breaking the co-operation between bystander T-cells and natural killer cells prevents the development of immunosuppression after traumatic skeletal muscle injury in mice

Nosocomial infections represent serious complications after traumatic or surgical injuries in intensive care units. The pathogenesis of the underlying immunosuppression is only incompletely understood. In the present study, we investigated whether injury interferes with the function of the adaptive...

Descripción completa

Detalles Bibliográficos
Autores principales: Wirsdörfer, Florian, Bangen, Jörg M., Pastille, Eva, Hansen, Wiebke, Flohé, Stefanie B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557401/
https://www.ncbi.nlm.nih.gov/pubmed/25609031
http://dx.doi.org/10.1042/CS20140835
_version_ 1782388499829227520
author Wirsdörfer, Florian
Bangen, Jörg M.
Pastille, Eva
Hansen, Wiebke
Flohé, Stefanie B.
author_facet Wirsdörfer, Florian
Bangen, Jörg M.
Pastille, Eva
Hansen, Wiebke
Flohé, Stefanie B.
author_sort Wirsdörfer, Florian
collection PubMed
description Nosocomial infections represent serious complications after traumatic or surgical injuries in intensive care units. The pathogenesis of the underlying immunosuppression is only incompletely understood. In the present study, we investigated whether injury interferes with the function of the adaptive immune system in particular with the differentiation of antigen-specific T helper (Th)-cell responses in vivo. We used a mouse model for traumatic gastrocnemius muscle injury. Ovalbumin (OVA), which served as a foreign model antigen, was injected into the hind footpads for determination of the differentiation of OVA-specific Th-cells in the draining popliteal lymph node (pLN). The release of interferon (IFN)-γ from OVA-specific Th-cells was impaired within 24 h after injury and this impairment persisted for at least 7 days. In contrast, the proliferation of OVA-specific Th-cells remained unaffected. Injury did not modulate the function of antigen-presenting cells (APCs) in the pLN. Adoptive transfer of total T-cells from pLNs of injured mice inhibited IFN-γ production by OVA-specific Th-cells in naive mice. Suppressed Th1 priming did not occur in lymphocyte-deficient mice after injury but was restored by administration of T-cells before injury. Moreover, the suppression of Th1 differentiation required the presence of natural killer (NK) cells that were recruited to the pLN after injury; this recruitment was dependent on lymphocytes, toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In summary, upon traumatic skeletal muscle injury T-cells and NK cells together prevent the development of protective Th1 immunity. Breaking this co-operation might be a novel approach to reduce the risk of infectious complications after injury.
format Online
Article
Text
id pubmed-4557401
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-45574012015-09-11 Breaking the co-operation between bystander T-cells and natural killer cells prevents the development of immunosuppression after traumatic skeletal muscle injury in mice Wirsdörfer, Florian Bangen, Jörg M. Pastille, Eva Hansen, Wiebke Flohé, Stefanie B. Clin Sci (Lond) Original Paper Nosocomial infections represent serious complications after traumatic or surgical injuries in intensive care units. The pathogenesis of the underlying immunosuppression is only incompletely understood. In the present study, we investigated whether injury interferes with the function of the adaptive immune system in particular with the differentiation of antigen-specific T helper (Th)-cell responses in vivo. We used a mouse model for traumatic gastrocnemius muscle injury. Ovalbumin (OVA), which served as a foreign model antigen, was injected into the hind footpads for determination of the differentiation of OVA-specific Th-cells in the draining popliteal lymph node (pLN). The release of interferon (IFN)-γ from OVA-specific Th-cells was impaired within 24 h after injury and this impairment persisted for at least 7 days. In contrast, the proliferation of OVA-specific Th-cells remained unaffected. Injury did not modulate the function of antigen-presenting cells (APCs) in the pLN. Adoptive transfer of total T-cells from pLNs of injured mice inhibited IFN-γ production by OVA-specific Th-cells in naive mice. Suppressed Th1 priming did not occur in lymphocyte-deficient mice after injury but was restored by administration of T-cells before injury. Moreover, the suppression of Th1 differentiation required the presence of natural killer (NK) cells that were recruited to the pLN after injury; this recruitment was dependent on lymphocytes, toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In summary, upon traumatic skeletal muscle injury T-cells and NK cells together prevent the development of protective Th1 immunity. Breaking this co-operation might be a novel approach to reduce the risk of infectious complications after injury. Portland Press Ltd. 2015-03-19 2015-06-01 /pmc/articles/PMC4557401/ /pubmed/25609031 http://dx.doi.org/10.1042/CS20140835 Text en © 2015 The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Licence (CC-BY)(http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Paper
Wirsdörfer, Florian
Bangen, Jörg M.
Pastille, Eva
Hansen, Wiebke
Flohé, Stefanie B.
Breaking the co-operation between bystander T-cells and natural killer cells prevents the development of immunosuppression after traumatic skeletal muscle injury in mice
title Breaking the co-operation between bystander T-cells and natural killer cells prevents the development of immunosuppression after traumatic skeletal muscle injury in mice
title_full Breaking the co-operation between bystander T-cells and natural killer cells prevents the development of immunosuppression after traumatic skeletal muscle injury in mice
title_fullStr Breaking the co-operation between bystander T-cells and natural killer cells prevents the development of immunosuppression after traumatic skeletal muscle injury in mice
title_full_unstemmed Breaking the co-operation between bystander T-cells and natural killer cells prevents the development of immunosuppression after traumatic skeletal muscle injury in mice
title_short Breaking the co-operation between bystander T-cells and natural killer cells prevents the development of immunosuppression after traumatic skeletal muscle injury in mice
title_sort breaking the co-operation between bystander t-cells and natural killer cells prevents the development of immunosuppression after traumatic skeletal muscle injury in mice
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557401/
https://www.ncbi.nlm.nih.gov/pubmed/25609031
http://dx.doi.org/10.1042/CS20140835
work_keys_str_mv AT wirsdorferflorian breakingthecooperationbetweenbystandertcellsandnaturalkillercellspreventsthedevelopmentofimmunosuppressionaftertraumaticskeletalmuscleinjuryinmice
AT bangenjorgm breakingthecooperationbetweenbystandertcellsandnaturalkillercellspreventsthedevelopmentofimmunosuppressionaftertraumaticskeletalmuscleinjuryinmice
AT pastilleeva breakingthecooperationbetweenbystandertcellsandnaturalkillercellspreventsthedevelopmentofimmunosuppressionaftertraumaticskeletalmuscleinjuryinmice
AT hansenwiebke breakingthecooperationbetweenbystandertcellsandnaturalkillercellspreventsthedevelopmentofimmunosuppressionaftertraumaticskeletalmuscleinjuryinmice
AT flohestefanieb breakingthecooperationbetweenbystandertcellsandnaturalkillercellspreventsthedevelopmentofimmunosuppressionaftertraumaticskeletalmuscleinjuryinmice