title: Dendritic Cell-Like Cells Accumulate in Regenerating Murine Skeletal Muscle after Injury and Boost Adaptive Immune Responses Only upon a Microbial Challenge.
abstract: Skeletal muscle injury causes a local sterile inflammatory response. In parallel, a state of immunosuppression develops distal to the site of tissue damage. Granulocytes and monocytes that are rapidly recruited to the site of injury contribute to tissue regeneration. In this study we used a mouse model of traumatic skeletal muscle injury to investigate the previously unknown role of dendritic cells (DCs) that accumulate in injured tissue. We injected the model antigen ovalbumin (OVA) into the skeletal muscle of injured or sham-treated mice to address the ability of these DCs in antigen uptake, migration, and specific T cell activation in the draining popliteal lymph node (pLN). Immature DC-like cells appeared in the skeletal muscle by 4 days after injury and subsequently acquired a mature phenotype, as indicated by increased expression of the costimulatory molecules CD40 and CD86. After the injection of OVA into the muscle, OVA-loaded DCs migrated into the pLN. The migration of DC-like cells from the injured muscle was enhanced in the presence of the microbial stimulus lipopolysaccharide at the site of antigen uptake and triggered an increased OVA-specific T helper cell type 1 (Th1) response in the pLN. Naïve OVA-loaded DCs were superior in Th1-like priming in the pLN when adoptively transferred into the skeletal muscle of injured mice, a finding indicating the relevance of the microenvironment in the regenerating skeletal muscle for increased Th1-like priming. These findings suggest that DC-like cells that accumulate in the regenerating muscle initiate a protective immune response upon microbial challenge and thereby overcome injury-induced immunosuppression.
authors.affiliation: Surgical Research, Department of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.|Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wirsdörfer
authors.affiliation: Surgical Research, Department of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Jörg M
authors.initials: JM
authors.lastname: Bangen
authors.affiliation: Surgical Research, Department of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.|Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Pastille
authors.affiliation: Surgical Research, Department of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schmitz
authors.affiliation: Surgical Research, Department of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Flohé
authors.affiliation: Institute of Molecular Medicine, Immunology, and Parasitology (IMMIP), University of Bonn, Bonn, Germany.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Schumak
authors.affiliation: Surgical Research, Department of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Stefanie B
authors.initials: SB
authors.lastname: Flohé
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004731:Endotoxins; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000276:immunology* / Q000293:injuries* / Q000382:microbiology; D010047:Ovalbumin; D012038:Regeneration / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D004731:Endotoxins; D008070:Lipopolysaccharides; D010047:Ovalbumin