title: Fibrocyte-like cells recruited to the spleen support innate and adaptive immune responses to acute injury or infection.
abstract: Bone marrow (BM)-derived fibrocytes are a population of CD45(+) and collagen Type I-expressing cells that migrate to the spleen and to target injured organs, such as skin, lungs, kidneys, and liver. While CD45(+)Col(+) fibrocytes contribute to collagen deposition at the site of injury, the role of CD45(+)Col(+) cells in spleen has not been elucidated. Here, we demonstrate that hepatotoxic injury (CCl(4)), TGF-β1, lipopolysaccharide, or infection with Listeria monocytogenes induce rapid recruitment of CD45(+)Col(+) fibrocyte-like cells to the spleen. These cells have a gene expression pattern that includes antimicrobial factors (myleoperoxidase, cathelicidin, and defensins) and MHC II at higher levels than found on quiescent or activated macrophages. The immune functions of these splenic CD45(+)Col(+) fibrocyte-like cells include entrapment of bacteria into extracellular DNA-based structures containing cathelicidin and presentation of antigens to naïve CD8(+) T cells to induce their proliferation. Stimulation of these splenic fibrocyte-like cells with granulocyte macrophage-colony stimulating factor or macrophage-colony stimulating factor induces downregulation of collagen expression and terminal differentiation into the dendritic cells or macrophage. Thus, splenic CD45(+)Col(+) cells are a population of rapidly mobilized BM-derived fibrocyte-like cells that respond to inflammation or infection to participate in innate and adaptive immune responses.
authors.affiliation: Department of Medicine, University of California, San Diego, 9500 Gilman Drive # 0702, La Jolla, CA 92093, USA. tkisseleva@ucsd.edu
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kisseleva
authors.forename: Maren
authors.initials: M
authors.lastname: von Köckritz-Blickwede
authors.forename: Donna
authors.initials: D
authors.lastname: Reichart
authors.forename: Shauna M
authors.initials: SM
authors.lastname: McGillvray
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wingender
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Glass
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: David A
authors.initials: DA
authors.lastname: Brenner
mesh_terms: D000208:Acute Disease; D056704:Adaptive Immunity / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002251:Carbon Tetrachloride; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D020869:Gene Expression Profiling; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D008103:Liver Cirrhosis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D013154:Spleen / Q000276:immunology* / Q000382:microbiology / Q000473:pathology* / Q000648:ultrastructure; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride; D017493:Leukocyte Common Antigens