Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers α-defensin production
Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers α-defensin production
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DOI：
10.1182/blood-2003-08-2820
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发表时间：
2004-09-15
期刊：
影响因子：
20.3
通讯作者：
Delneste, Y
中科院分区：
文献类型：
--
作者：
Chalifour, A;Jeannin, P;Delneste, Y
虽然人类CD56(+)CD3（-）自然杀伤（NK）细胞参与了针对微生物的免疫应答，但它们直接识别病原体并被病原体激活的能力尚不清楚。这些细胞编码toll样受体（TLR）家族的成员，参与识别病原体相关分子模式（PAMPs）的先天细胞激活。因此，我们评估了分别通过TLR2和TLR5发出信号的肺炎克雷伯菌外膜蛋白A （KpOmpA）和鞭毛蛋白2种细菌蛋白PAMPs是否可以直接刺激人NK细胞。这些蛋白诱导NK细胞产生干扰素- γ (ifn - γ)，并与白细胞介素-2 （IL-2）和炎性原细胞因子协同作用，诱导pamp活化。使用CD56(+)CD3(+)（表达nkr） T细胞获得了类似的结果。来自TLR2（-/-）小鼠的NK细胞对KpOmpA的反应下降，表明TLR参与了这种作用。防御素是主要由上皮细胞和中性粒细胞表达的抗菌肽，它们破坏细菌膜，导致病原体死亡。这些蛋白诱导NK细胞产生干扰素- γ (ifn - γ)，并与白细胞介素-2 （IL-2）和炎性原细胞因子协同作用，诱导pamp活化。使用CD56(+)CD3(+)（表达nkr） T细胞获得了类似的结果。来自TLR2（-/-）小鼠的NK细胞对KpOmpA的反应下降，表明TLR参与了这种作用。防御素是主要由上皮细胞和中性粒细胞表达的抗菌肽，它们破坏细菌膜，导致病原体死亡。我们发现NK细胞和表达NK的T细胞组成性地表达α -防御素，KpOmpA和鞭毛蛋白能快速诱导α -防御素的释放。这些数据首次证明，高纯度NK细胞通过tlr直接识别和响应病原体成分，并证明防御素是一种新的直接细胞毒性途径，参与NK细胞介导的对微生物的保护。(C) 2004年由美国血液病学会出版。
Although human CD56(+)CD3(-) natural killer (NK) cells participate in immune responses against microorganisms, their capacity to directly recognize and be activated by pathogens remains unclear. These cells encode members of the Toll-like receptor (TLR) family, involved in innate cell activation on recognition of pathogen-associated molecular patterns (PAMPs). We therefore evaluated whether the 2 bacterial protein PAMPs, the outer membrane protein A from Klebsiella pneumoniae (KpOmpA) and flagellin, which signal through TLR2 and TLR5, respec-tively, may directly stimulate human NK cells. These proteins induce interferon-gamma (IFN-gamma) production by NK cells and synergize with interleukin-2 (IL-2) and proin-flammatory cytokines in PAMP-induced activation. Similar results were obtained using CD56(+)CD3(+) (NKR-expressing) T cells. NK cells from TLR2(-/-) mice fall to respond to KpOmpA, demonstrating TLR involvement in this effect. Defensins are antimicrobial peptides expressed mainly by epithelial cells and neutrophils that disrupt the bacterial membrane, leading to pathogen death. We show that NK cells These proteins induce interferon-gamma (IFN-gamma) production by NK cells and synergize with interleukin-2 (IL-2) and proin-flammatory cytokines in PAMP-induced activation. Similar results were obtained using CD56(+)CD3(+) (NKR-expressing) T cells. NK cells from TLR2(-/-) mice fall to respond to KpOmpA, demonstrating TLR involvement in this effect. Defensins are antimicrobial peptides expressed mainly by epithelial cells and neutrophils that disrupt the bacterial membrane, leading to pathogen death. We show that NK cells and NKR-expressing T cells constitutively express alpha-defensins and that KpOmpA and flagellin rapidly induce their release. These data demonstrate for the first time that highly purified NK cells directly recognize and respond to pathogen components through TLRs and evidence defensins as a novel and direct cytotoxic pathway involved in NK cell-mediated protection against microorganisms. (C) 2004 by The American Society of Hematology.