Human uterine NK cells interact with uterine macrophages via NKG2D upon stimulation with PAMPs

Am J Reprod Immunol. 2009 Jan;61(1):52-61. doi: 10.1111/j.1600-0897.2008.00661.x.


Problem: The initiation of an immune response often involves the cooperation of various innate immune cells. In the human endometrium, uterine natural killer (uNK) cells and uterine macrophages are present in significant numbers and in close proximity, yet how they cooperatively respond to infectious challenge is poorly understood.

Method of study: Primary autologous uNK cells and macrophages were co-cultured to determine functional interactions after stimulation with pathogen-associated molecular patterns.

Results: After stimulation by polyI:C, human uNK cells interact with autologous uterine macrophages and produce interferon-gamma in an NKG2D-dependent manner. Stimulated primary uterine macrophages up-regulated the expression of MHC Class I chain-related protein A (MICA), but expression of the cognate receptor NKG2D remained unchanged on uNK cells, even in the presence of cytokines.

Conclusion: This study demonstrates that the NKG2D-MICA interaction is an important molecular mechanism that is involved in the innate immune response to microbial signals in the human uterine endometrium.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • CD56 Antigen / metabolism
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Lipopolysaccharide Receptors / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily K / immunology*
  • Poly I-C / pharmacology
  • Toll-Like Receptor 3 / immunology
  • Toll-Like Receptor 3 / metabolism
  • Up-Regulation
  • Uterus / drug effects
  • Uterus / immunology*
  • Uterus / metabolism


  • CD56 Antigen
  • KLRK1 protein, human
  • Lipopolysaccharide Receptors
  • NK Cell Lectin-Like Receptor Subfamily K
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Interferon-gamma
  • Poly I-C