A novel lipopeptide from skin commensal activates TLR2/CD36-p38 MAPK signaling to increase antibacterial defense against bacterial infection.
A novel lipopeptide from skin commensal activates TLR2/CD36-p38 MAPK signaling to increase antibacterial defense against bacterial infection.
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皮肤共生体中的一种新型脂肽可激活 TLR2/CD36-p38 MAPK 信号传导以增强针对细菌感染的抗菌防御
DOI：
10.1371/journal.pone.0058288
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lai Y
中科院分区：
文献类型：
--
作者：
Li D;Lei H;Li Z;Li H;Wang Y;Lai Y
表皮葡萄球菌（Staphylococcus epidermidis，S.epidermidis）通过直接产生或刺激宿主产生抗菌肽（antimicrobial peptides，AMP）而发挥重要的保护作用。虽然已经鉴定了来自表皮葡萄球菌的几种AMP，但是刺激宿主产生AMP的分子仍然是未知的。在这里，我们证明了一种新的脂肽（命名为LP 01）从表皮葡萄球菌培养基中纯化具有独特的结构与二十一烷酸（21个碳）结合的赖氨酸11的肽链。在体外，LP 01增加了新生儿人表皮角质形成细胞（NHEK）中β-防御素2（hBD 2）和hBD 3的表达，导致细胞裂解物抑制金黄色葡萄球菌生长的能力增加。在体内，LP 01诱导小鼠β-防御素4（mBD 4）的表达以降低皮肤中局部金黄色葡萄球菌的存活和肝脏中全身金黄色葡萄球菌的存活。LPOl对β-防御素的诱导依赖于TLR 2，因为Tlr 2缺陷小鼠的mBD 4减少。结果表明，正常表皮葡萄球菌脂肽LP 01通过激活TLR 2/CD 36-p38 MAPK，促进hBD 2和hBD 3的表达，从而增强抗菌防御作用。
Staphylococcus epidermidis (S.epidermidis) plays important protective roles by directly producing or by stimulating hosts to produce antimicrobial peptides (AMPs) against pathogenic infections. Although several AMPs from S.epidermidis have been identified, molecules that stimulate hosts to produce AMPs remain largly unknown. Here we demonstrate that a new lipopeptide (named LP01) purified from S.epidermidis culture media has a unique structure with heneicosanoic acid (21 carbons) binding to lysine11 of a peptide chain. In vitro LP01 increased the expression of β-defensin 2(hBD2) and hBD3 in neonatal human epidermal keratinocytes(NHEK), leading to increased capacity of cell lysates to inhibit the growth of S.aureus. In vivo LP01 induced the expression of mouse β-defensin 4(mBD4) to decrease the survival of local S.aureus in skin and systemic S.aureus survival in liver. The induction of beta-defensins by LP01 was dependent on TLR2 as Tlr2-deficient mice had decreased mBD4. Furthermore, knockdown of CD36 decreased the expression of hBD2 and hBD3, and p38 MAPK inhibitor significantly inhibited the expression of hBDs induced by LP01.Taken together, these findings demonstrate that lipopeptide LP01 from normal commensal S.epidermidis increases antimicrobial peptide hBD2 and hBD3 expression via the activation of TLR2/CD36-p38 MAPK, thus enhancing antimicrobial defense against pathogenic infections.
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影响因子：
64.8
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