Eriksson Mikael, Meadows Sarah K, Basu Satarupa, Mselle Teddy F, Wira Charles R, Sentman Charles L
Department of Microbiology and Immunology, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA.
J Immunol. 2006 May 15;176(10):6219-24. doi: 10.4049/jimmunol.176.10.6219.
The human endometrium (EM) contains macrophages, NK cells, T cells, B cells, and neutrophils in contact with a variety of stromal and epithelial cells. The interplay between these different cell types and their roles in defense against pathogen invasion in this specialized tissue are important for controlling infection and reproduction. TLRs are a family of receptors able to recognize conserved pathogen-associated molecular patterns. In this study, we determined the expression of TLRs on uterine NK (uNK) cells from the human EM and the extent to which uNK cells responded to TLR agonist stimulation. uNK cells expressed TLRs 2, 3, and 4, and produced IFN-gamma when total human endometrial cells were stimulated with agonists to TLR2 or TLR3 (peptidoglycan or poly(I:C), respectively). Activated uNK cell clones produced IFN-gamma upon stimulation with peptidoglycan or poly(I:C). However, purified uNK cells did not respond directly to TLR agonists, but IFN-gamma was produced by uNK cells in response to TLR stimulation when cocultured with APCs. These data indicate that uNK cells express TLRs and that they can respond to TLR agonists within EM by producing IFN-gamma. These data also indicate that the uNK cells do not respond directly to TLR stimulation, but rather their production of IFN-gamma is dependent upon interactions with other cells within EM.
人类子宫内膜（EM）含有巨噬细胞、自然杀伤（NK）细胞、T细胞、B细胞和中性粒细胞，它们与多种基质细胞和上皮细胞相互接触。这些不同细胞类型之间的相互作用及其在这种特殊组织中抵御病原体入侵的作用对于控制感染和生殖至关重要。Toll样受体（TLR）是一类能够识别保守的病原体相关分子模式的受体。在本研究中，我们测定了人类EM中子宫NK（uNK）细胞上TLR的表达以及uNK细胞对TLR激动剂刺激的反应程度。uNK细胞表达TLR2、TLR3和TLR4，当用人子宫内膜细胞用TLR2或TLR3激动剂（分别为肽聚糖或聚肌苷酸:聚胞苷酸）刺激时，会产生γ干扰素。激活的uNK细胞克隆在用肽聚糖或聚肌苷酸:聚胞苷酸刺激时会产生γ干扰素。然而，纯化的uNK细胞对TLR激动剂无直接反应，但当与抗原呈递细胞（APC）共培养时，uNK细胞会因TLR刺激而产生γ干扰素。这些数据表明uNK细胞表达TLR，并且它们可以通过产生γ干扰素对EM内的TLR激动剂作出反应。这些数据还表明uNK细胞对TLR刺激无直接反应，而是其γ干扰素的产生依赖于与EM内其他细胞的相互作用。
