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.
abstract: 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.
authors.affiliation: *Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wirsdörfer
authors.affiliation: *Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Jörg M
authors.initials: JM
authors.lastname: Bangen
authors.affiliation: *Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Pastille
authors.affiliation: ‡Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hansen
authors.affiliation: *Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Stefanie B
authors.initials: SB
authors.lastname: Flohé
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D024201:Bystander Effect / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000276:immunology* / Q000293:injuries; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma; D010047:Ovalbumin