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

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