ORIGINAL ARTICLE: Human Uterine NK Cells Interact with Uterine Macrophages via NKG2D upon Stimulation with PAMPs


Charles L. Sentman, Department of Microbiology & Immunology, Dartmouth Medical School, 6W Borwell Bldg, One Medical Center Drive, Lebanon, NH 03756, USA.
E-mail: charles.sentman@dartmouth.edu


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-γ 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.