The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands
The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands
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DOI：
10.1093/intimm/dxl107
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发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Bals, Robert
中科院分区：
文献类型：
--
作者：
Kandler, Kerstin;Shaykhiev, Renat;Bals, Robert
内源性抗菌肽LL-37/hCAP-18是机体表面先天性宿主防御系统的效应分子。除了其直接的抗微生物活性外，该肽还与不同的细胞类型相互作用。树突状细胞（Dendritic cells，DCs）在粘膜宿主防御中起着重要作用。该研究的目的是确定LL-37是否调节DC对病原体相关分子模式的反应。单核细胞衍生的DC用Toll样受体（TLR）配体LPS、脂磷壁酸和鞭毛蛋白刺激。我们测量了DC成熟的经典标志物，并测定了DC激活T细胞应答的能力。与LL-37共孵育导致DC的活化受到抑制。释放的IL-6、IL-12 p70和TNF-α水平以及HLA-DR、CD 80、CD 83、CD 86和趋化因子受体CCR 7的表面表达降低。在LPS暴露期间DC暴露于LL-37诱导共培养的幼稚T细胞产生较少的IL-2和IFN-γ并降低其增殖。记忆T细胞对回忆抗原的反应也降低了。总之，我们证明抗微生物肽LL-37抑制TLR配体对DC的激活。我们认为LL-37是先天性和适应性免疫系统交叉处宿主防御反应的调节剂。
The endogenous anti-microbial peptide LL-37/hCAP-18 is an effector molecule of the innate host defense system at surfaces of the body. Besides its direct anti-microbial activity, the peptide interacts with different cell types. Dendritic cells (DCs) play a central role in mucosal host defense. It was the aim of the study to determine whether LL-37 modulates the response of DCs to pathogen-associated molecular patterns. Monocyte-derived DCs were stimulated with the Toll-like receptors (TLRs) ligands LPS, lipoteichoic acid and flagellin. We measured classical markers of DC maturation and assayed the ability of the DCs to activate T cell responses. Co-incubation with LL-37 resulted in suppressed activation of DCs. Levels of released IL-6, IL-12p70 and TNF-alpha and surface expression of HLA-DR, CD80, CD83, CD86 and the chemokine receptor CCR7 were decreased. Exposure of DCs to LL-37 during LPS exposure induced co-cultured naive T cells to produce less IL-2 and IFN-gamma and decreased their proliferation. The response of memory T cells to a recall antigen was also decreased. In conclusion, we demonstrate that the anti-microbial peptide LL-37 inhibits the activation of DCs by TLR ligands. We propose that LL-37 is a regulator of host defense responses at the intersection of innate and adaptive immune systems.