Interaction between dendritic cells and natural killer cells during pregnancy in mice

  • Sandra M. Blois
  • Gabriela Barrientos
  • Mariana G. Garcia
  • Arif S. Orsal
  • Mareike Tometten
  • Rosalia I. Cordo-Russo
  • Burghard F. Klapp
  • Angela Santoni
  • Nelson Fernández
  • Peter Terness
  • Petra C. Arck
Original Article

DOI: 10.1007/s00109-008-0342-2

Cite this article as:
Blois, S.M., Barrientos, G., Garcia, M.G. et al. J Mol Med (2008) 86: 837. doi:10.1007/s00109-008-0342-2

Abstract

A complex regulation of innate and adaptive immune responses at the maternal fetal interface promotes tolerance of trophoblast cells carrying paternally derived antigens. Such regulatory functions involve uterine dendritic cells (uDC) and natural killer (uNK) cells. The existence of a NK and DC “cross talk” has been revealed in various experimental settings; its biological significance ranging from cooperative stimulation to cell lysis. Little is known about the presence or role of NK and DC cross talk at the maternal fetal interface. The present study shows that mouse NK and DC interactions are subject to modulation by trophoblast cells in vitro. This interaction promotes a tolerogenic microenvironment characterized by downregulation of the expression of activation markers on uNK cells and uDC and dominance of Th2 cytokines. NK and DC interactions would also influence uterine cell proliferation and this process would be strongly modulated by trophoblast-derived signals. Indeed; while low proliferation rates were observed upon regular coculture allowing direct contact between uterine cells and trophoblasts, incubation in a transwell culture system markedly increased uterine cell proliferation suggesting that soluble factors are key mediators in the molecular “dialog” between the mother and the conceptus during the establishment of mouse pregnancy. Our data further reveal that the regulatory functions of trophoblast cells associated with tolerance induction are impaired in high abortion murine matings. Interestingly, we observed that secretion of interleukin-12p70 by uDC is dramatically abrogated in the presence of uNK cells. Taken together, our results provide the first evidence that a delicate balance of interactions involving NK cells, DC, and trophoblasts at the mouse maternal fetal interface supports a successful pregnancy outcome.

Keywords

Natural killer cells Dendritic cells Uterus Tolerance Pregnancy Mice 

Abbreviations

DC

dendritic cells

NK

natural killer cells

Tro

trophoblast

IDO

indoleamine 2,3 dioxigenase

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Sandra M. Blois
    • 1
  • Gabriela Barrientos
    • 1
  • Mariana G. Garcia
    • 1
  • Arif S. Orsal
    • 1
  • Mareike Tometten
    • 1
  • Rosalia I. Cordo-Russo
    • 1
  • Burghard F. Klapp
    • 1
  • Angela Santoni
    • 3
  • Nelson Fernández
    • 2
  • Peter Terness
    • 4
  • Petra C. Arck
    • 1
  1. 1.Charité Centrum 12 für Innere Medizin und DermatologieUniversity Medicine of BerlinBerlinGermany
  2. 2.Department of Biological SciencesUniversity of EssexColchesterUK
  3. 3.Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-BolognettiUniversity ‘La Sapienza’RomeItaly
  4. 4.Department of Transplantation ImmunologyInstitute for ImmunologyHeidelbergGermany

Personalised recommendations