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Fibrocyte-like cells recruited to the spleen support innate and adaptive immune responses to acute injury or infection

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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 (CCl4), 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.

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Abbreviations

Sp. F:

CD45+Col+ fibrocyte-like cells in spleen

MΦ:

Macrophages

SC:

Hepatic stellate cells

References

  1. Quan TE, Cowper S, Wu SP, Bockenstedt LK, Bucala R (2004) Circulating fibrocytes: collagen-secreting cells of the peripheral blood. Int J Biochem Cell Biol 36:598–606. doi:10.1016/j.biocel.2003.10.005

    Article  PubMed  CAS  Google Scholar 

  2. Phillips RJ, Burdick MD, Hong K, Lutz MA, Murray LA, Xue YY, Belperio JA, Keane MP, Strieter RM (2004) Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest 114:438–446. doi:10.1172/JCI20997

    PubMed  CAS  Google Scholar 

  3. Hashimoto N, Jin H, Liu T, Chensue SW, Phan SH (2004) Bone marrow-derived progenitor cells in pulmonary fibrosis. J Clin Invest 113:243–252

    PubMed  CAS  Google Scholar 

  4. Galan A, Cowper SE, Bucala R (2006) Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy). Curr Opin Rheumatol 18:614–617. doi:10.1097/01.bor.0000245725.94887.8d

    Article  PubMed  Google Scholar 

  5. Kisseleva T, Brenner DA (2008) Fibrogenesis of parenchymal organs. Proc Am Thorac Soc 5:338–342. doi:10.1513/pats.200711-168DR

    Article  PubMed  Google Scholar 

  6. Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A (1994) Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1:71–81

    PubMed  CAS  Google Scholar 

  7. Kisseleva T, Uchinami H, Feirt N, Quintana-Bustamante O, Segovia JC, Schwabe RF, Brenner DA (2006) Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis. J Hepatol 45:429–438

    Article  PubMed  CAS  Google Scholar 

  8. Sakai N, Wada T, Yokoyama H, Lipp M, Ueha S, Matsushima K, Kaneko S (2006) Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis. Proc Natl Acad Sci USA 103:14098–14103

    Article  PubMed  CAS  Google Scholar 

  9. Curnow SJ, Fairclough M, Schmutz C, Kissane S, Denniston AK, Nash K, Buckley CD, Lord JM, Salmon M (2010) Distinct types of fibrocyte can differentiate from mononuclear cells in the presence and absence of serum. PLoS One 5:e9730. doi:10.1371/journal.pone.0009730

    Article  PubMed  Google Scholar 

  10. Chesney J, Bacher M, Bender A, Bucala R (1997) The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T cells in situ. Proc Natl Acad Sci USA 94:6307–6312

    Article  PubMed  CAS  Google Scholar 

  11. Balmelli C, Ruggli N, McCullough K, Summerfield A (2005) Fibrocytes are potent stimulators of anti-virus cytotoxic T cells. J Leukoc Biol 77:923–933. doi:10.1189/jlb.1204701

    Article  PubMed  CAS  Google Scholar 

  12. Uehara H, Nakagawa T, Katsuno T, Sato T, Isono A, Noguchi Y, Saito Y (2009) Emergence of fibrocytes showing morphological changes in the inflamed colonic mucosa. Dig Dis Sci 55:253–260. doi:10.1007/s10620-009-0730-7

    Article  PubMed  Google Scholar 

  13. Carmona R, Cano E, Grueso E, Ruiz-Villalba A, Bera T, Gaztambide J, Segovia JC, Munoz-Chapuli R (2010) Peritoneal repairing cells: a type of bone marrow-derived progenitor cells involved in mesothelial regeneration. J Cell Mol Med. doi:10.1111/j.1582-4934.2010.01087.x

    Google Scholar 

  14. Yata Y, Scanga A, Gillan A, Yang L, Reif S, Breindl M, Brenner DA, Rippe RA (2003) DNase I-hypersensitive sites enhance alpha1(I) collagen gene expression in hepatic stellate cells. Hepatology 37:267–276. doi:10.1053/jhep.2003.50067

    Article  PubMed  CAS  Google Scholar 

  15. Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA, Schwabe RF (2007) TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med 13:1324–1332. doi:10.1038/nm1663

    Article  PubMed  CAS  Google Scholar 

  16. Takebayashi K, Koboziev I, Ostanin DV, Gray L, Karlsson F, Robinson-Jackson SA, Kosloski-Davidson M, Dooley AB, Zhang S, Grisham MB (2011) Role of the gut-associated and secondary lymphoid tissue in the induction of chronic colitis. Inflamm Bowel Dis 17:268–278. doi:10.1002/ibd.21447

    Article  PubMed  Google Scholar 

  17. Karnovsky MJ (1964) The localization of cholinesterase activity in rat cardiac muscle by electron microscopy. J Cell Biol 23:217–232

    Article  PubMed  CAS  Google Scholar 

  18. Jia T, Serbina NV, Brandl K, Zhong MX, Leiner IM, Charo IF, Pamer EG (2008) Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection. J Immunol 180:6846–6853

    PubMed  CAS  Google Scholar 

  19. Pilling D, Fan T, Huang D, Kaul B, Gomer RH (2009) Identification of markers that distinguish monocyte-derived fibrocytes from monocytes, macrophages, and fibroblasts. PLoS ONE 4:e7475. doi:10.1371/journal.pone.0007475

    Article  PubMed  Google Scholar 

  20. Rhodin JAG (1975) An atlas of histology. Oxford University Press, New York, London, Toronto

    Google Scholar 

  21. Gebhardt C, Nemeth J, Angel P, Hess J (2006) S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol 72:1622–1631. doi:10.1016/j.bcp.2006.05.017

    Article  PubMed  CAS  Google Scholar 

  22. Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, Pestonjamasp V, Piraino J, Huttner K, Gallo RL (2001) Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414:454–457. doi:10.1038/35106587

    Article  PubMed  CAS  Google Scholar 

  23. Dustin ML, Tseng SY, Varma R, Campi G (2006) T cell-dendritic cell immunological synapses. Curr Opin Immunol 18:512–516. doi:10.1016/j.coi.2006.05.017

    Article  PubMed  CAS  Google Scholar 

  24. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532–1535. doi:10.1126/science.1092385

    Article  PubMed  CAS  Google Scholar 

  25. von Kockritz-Blickwede M, Goldmann O, Thulin P, Heinemann K, Norrby-Teglund A, Rohde M, Medina E (2008) Phagocytosis-independent antimicrobial activity of mast cells by means of extracellular trap formation. Blood 111:3070–3080. doi:10.1182/blood-2007-07-104018

    Article  Google Scholar 

  26. Yousefi S, Gold JA, Andina N, Lee JJ, Kelly AM, Kozlowski E, Schmid I, Straumann A, Reichenbach J, Gleich GJ, Simon HU (2008) Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat Med 14:949–953. doi:10.1038/nm.1855

    Article  PubMed  CAS  Google Scholar 

  27. Chow OA, von Köckritz-Blickwede M, Bright AT, Hensler ME, Zinkernagel AS, Cogen AL, Gallo RL, Monestier M, Wang Y, Glass CK, Nizet V (2010) Statins enhance formation of phagocyte extracellular traps. Cell Host Microbe 8:445–454

    Article  PubMed  CAS  Google Scholar 

  28. von Kockritz-Blickwede M, Nizet V (2009) Innate immunity turned inside-out: antimicrobial defense by phagocyte extracellular traps. J Mol Med 87:775–783. doi:10.1007/s00109-009-0481-0

    Article  Google Scholar 

  29. Wartha F, Henriques-Normark B (2008) ETosis: a novel cell death pathway. Sci Signal 1:pe25

    Article  PubMed  Google Scholar 

  30. Borregaard N (1997) Development of neutrophil granule diversity. Ann NY Acad Sci 832:62–68

    Article  PubMed  CAS  Google Scholar 

  31. Serbina NV, Jia T, Hohl TM, Pamer EG (2008) Monocyte-mediated defense against microbial pathogens. Annu Rev Immunol 26:421–452. doi:10.1146/annurev.immunol.26.021607.090326

    Article  PubMed  CAS  Google Scholar 

  32. Niedermeier M, Reich B, Rodriguez Gomez M, Denzel A, Schmidbauer K, Gobel N, Talke Y, Schweda F, Mack M (2009) CD4+ T cells control the differentiation of Gr1+ monocytes into fibrocytes. Proc Natl Acad Sci USA 106:17892–17897. doi:10.1073/pnas.0906070106

    Article  PubMed  CAS  Google Scholar 

  33. Legrand D, Elass E, Carpentier M, Mazurier J (2005) Lactoferrin: a modulator of immune and inflammatory responses. Cell Mol Life Sci 62:2549–2559

    Article  PubMed  CAS  Google Scholar 

  34. Rehaume LM, Hancock RE (2008) Neutrophil-derived defensins as modulators of innate immune function. Crit Rev Immunol 28:185–200

    PubMed  CAS  Google Scholar 

  35. HogenEsch H, Dunham A, Seymour R, Renninger M, Sundberg JP (2006) Expression of chitinase-like proteins in the skin of chronic proliferative dermatitis (cpdm/cpdm) mice. Exp Dermatol 15:808–814

    Article  PubMed  CAS  Google Scholar 

  36. Kraus D, Peschel A (2008) Staphylococcus aureus evasion of innate antimicrobial defense. Future Microbiol 3:437–451. doi:10.2217/17460913.3.4.437

    Article  PubMed  CAS  Google Scholar 

  37. Brinkmann V, Zychlinsky A (2007) Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol 5:577–582. doi:10.1038/nrmicro1710

    Article  PubMed  CAS  Google Scholar 

  38. Bellini A, Mattoli S (2007) The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses. Lab Invest 87:858–870

    Article  PubMed  CAS  Google Scholar 

  39. Laird DJ, von Andrian UH, Wagers AJ (2008) Stem cell trafficking in tissue development, growth, and disease. Cell 132:612–630. doi:10.1016/j.cell.2008.01.041

    Article  PubMed  CAS  Google Scholar 

  40. Steinbakk M, Naess-Andresen CF, Lingaas E, Dale I, Brandtzaeg P, Fagerhol MK (1990) Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin. Lancet 336:763–765

    Article  PubMed  CAS  Google Scholar 

  41. Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319:962–965. doi:10.1126/science.1152449

    Article  PubMed  CAS  Google Scholar 

  42. Schnoor M, Cullen P, Lorkowski J, Stolle K, Robenek H, Troyer D, Rauterberg J, Lorkowski S (2008) Production of type VI collagen by human macrophages: a new dimension in macrophage functional heterogeneity. J Immunol 180:5707–5719

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Stephen Shoenenberger, Ekihiro Seki, Marc Monestier, Kristi Gordon, Peggy Okeefe, Neal Sekiya, and Karin Diggle for their support. Supported by the National Institutes of Health (GM41804, AA15055, DK72237, and AI077780) and the American Liver Foundation (2006 Liver Scholar Research Award). M.v.K-B. was supported by the Deutsche Akademie der Naturforscher Leopoldina (BMBF-LDP 9901/8-181).

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Authors and Affiliations

  1. Department of Medicine, University of California, San Diego, 9500 Gilman Drive # 0702, La Jolla, CA, 92093, USA

    Tatiana Kisseleva & David A. Brenner

  2. Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA

    Maren von Köckritz-Blickwede, Shauna M. McGillvray & Victor Nizet

  3. Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, 92093, USA

    Donna Reichart & Christopher K. Glass

  4. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, 92093, USA

    Victor Nizet

  5. La Jolla Institute of Allergy and Immunology, La Jolla, CA, 92037, USA

    Gerhard Wingender & Mitchell Kronenberg

  6. Department of Physiological Chemistry, University of Veterinary Medicine, Hannover, Germany

    Maren von Köckritz-Blickwede

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  1. Tatiana Kisseleva
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  9. David A. Brenner
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Correspondence to Tatiana Kisseleva.

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Kisseleva, T., von Köckritz-Blickwede, M., Reichart, D. et al. Fibrocyte-like cells recruited to the spleen support innate and adaptive immune responses to acute injury or infection. J Mol Med 89, 997–1013 (2011). https://doi.org/10.1007/s00109-011-0756-0

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