Investigating Human Dendritic Cell Immune Responses to Borrelia burgdorferi

  • Lauren M. K. Mason
  • Joppe W. R. Hovius
Part of the Methods in Molecular Biology book series (MIMB, volume 1690)


Dendritic cells (DCs) are professional antigen-presenting cells that recognize and phagocytose pathogens, and help to orchestrate adaptive immune responses to combat them. DCs are abundant in the skin where Borrelia burgdorferi first enters the body during a tick bite, and are thus critical in determining the initial stages of the innate and adaptive immune responses against Borrelia. Here, we describe two methods to study the response of DCs to Borrelia; an in vitro approach using monocyte-derived DCs (moDCs) and an ex vivo approach using a human skin model.

Key words

DCs moDCs Skin model Borrelia Lyme borreliosis 



We are very grateful to Ard Nijhof for providing I. ricinus salivary gland extract, Justin Radolf and Juan Salazar for providing frozen Treponema pallidum, and Henry de Vries for providing human syphilitic serum for the experiments shown in Fig. 1. This work was supported by a “Veni” grant (91611065) from JWH received from The Netherlands Organisation for health research and development (ZonMw).


  1. 1.
    Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392(6673):245–252. doi: 10.1038/32588 CrossRefPubMedGoogle Scholar
  2. 2.
    Mason LM, Herkes EA, Krupna-Gaylord MA, Oei A, van der Poll T, Wormser GP, Schwartz I, Petzke MM, Hovius JW (2015) Borrelia burgdorferi clinical isolates induce human innate immune responses that are not dependent on genotype. Immunobiology 220(10):1141–1150. doi: 10.1016/j.imbio.2015.06.006 CrossRefPubMedGoogle Scholar
  3. 3.
    Mason LM, Veerman CC, Geijtenbeek TB, Hovius JW (2014) Menage a trois: Borrelia, dendritic cells, and tick saliva interactions. Trends Parasitol 30(2):95–103. doi: 10.1016/ CrossRefPubMedGoogle Scholar
  4. 4.
    Filgueira L, Nestle FO, Rittig M, Joller HI, Groscurth P (1996) Human dendritic cells phagocytose and process Borrelia burgdorferi. J Immunol 157(7):2998–3005PubMedGoogle Scholar
  5. 5.
    Hovius JW, de Jong MA, den Dunnen J, Litjens M, Fikrig E, van der Poll T, Gringhuis SI, Geijtenbeek TB (2008) Salp15 binding to DC-SIGN inhibits cytokine expression by impairing both nucleosome remodeling and mRNA stabilization. PLoS Pathog 4(2):e31. doi: 10.1371/journal.ppat.0040031 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Suhonen J, Komi J, Soukka J, Lassila O, Viljanen MK (2003) Interaction between Borrelia burgdorferi and immature human dendritic cells. Scand J Immunol 58(1):67–75CrossRefPubMedGoogle Scholar
  7. 7.
    Romani N, Gruner S, Brang D, Kampgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G (1994) Proliferating dendritic cell progenitors in human blood. J Exp Med 180(1):83–93CrossRefPubMedGoogle Scholar
  8. 8.
    de Gruijl TD, Sombroek CC, Lougheed SM, Oosterhoff D, Buter J, van den Eertwegh AJ, Scheper RJ, Pinedo HM (2006) A postmigrational switch among skin-derived dendritic cells to a macrophage-like phenotype is predetermined by the intracutaneous cytokine balance. J Immunol 176(12):7232–7242CrossRefPubMedGoogle Scholar
  9. 9.
    Flacher V, Tripp CH, Stoitzner P, Haid B, Ebner S, Del Frari B, Koch F, Park CG, Steinman RM, Idoyaga J, Romani N (2010) Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis. J Invest Dermatol 130(3):755–762. doi: 10.1038/jid.2009.343 CrossRefPubMedGoogle Scholar
  10. 10.
    Schneider LP, Schoonderwoerd AJ, Moutaftsi M, Howard RF, Reed SG, de Jong EC, Teunissen MB (2012) Intradermally administered TLR4 agonist GLA-SE enhances the capacity of human skin DCs to activate T cells and promotes emigration of Langerhans cells. Vaccine 30(28):4216–4224. doi: 10.1016/j.vaccine.2012.04.051 CrossRefPubMedGoogle Scholar
  11. 11.
    Mathes SH, Ruffner H, Graf-Hausner U (2014) The use of skin models in drug development. Adv Drug Deliv Rev 69-70:81–102. doi: 10.1016/j.addr.2013.12.006 CrossRefPubMedGoogle Scholar
  12. 12.
    Mason LM, Wagemakers A, van't Veer C, Oei A, van der Pot WJ, Ahmed K, van der Poll T, Geijtenbeek TB, Hovius JW (2016) Borrelia burgdorferi induces TLR2-mediated migration of activated dendritic cells in an ex vivo human skin model. PLoS One 11(10):e0164040. doi: 10.1371/journal.pone.0164040 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Petzke MM, Brooks A, Krupna MA, Mordue D, Schwartz I (2009) Recognition of Borrelia burgdorferi, the Lyme disease spirochete, by TLR7 and TLR9 induces a type I IFN response by human immune cells. J Immunol 183(8):5279–5292. doi: 10.4049/jimmunol.0901390 CrossRefPubMedGoogle Scholar
  14. 14.
    Silver AC, Dunne DW, Zeiss CJ, Bockenstedt LK, Radolf JD, Salazar JC, Fikrig E (2013) MyD88 deficiency markedly worsens tissue inflammation and bacterial clearance in mice infected with Treponema pallidum, the agent of syphilis. PLoS One 8(8):e71388. doi: 10.1371/journal.pone.0071388 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  1. 1.Center for Experimental and Molecular MedicineAcademic Medical CenterAmsterdamThe Netherlands
  2. 2.Division of Infectious DiseasesAcademic Medical CenterAmsterdamThe Netherlands

Personalised recommendations