Control of Pseudomonas aeruginosa skin infections in mice is mast cell-dependent
Control of Pseudomonas aeruginosa skin infections in mice is mast cell-dependent
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DOI：
10.2353/ajpath.2007.060770
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发表时间：
2007-06-01
影响因子：
6
通讯作者：
Maurer, Marcus
中科院分区：
文献类型：
--
作者：
Siebenhaar, Frank;Syska, Wolfgang;Maurer, Marcus
肥大细胞（MC）最近已被证明是必不可少的诱导有效的免疫反应，在小鼠败血症。为了探索MC是否也有助于控制细菌性皮肤感染，我们研究了铜绿假单胞菌（PA）在遗传MC缺陷Kit（W）/Kit（W-v）小鼠、正常Kit（+/+）小鼠和MC重建Kit（W）/Kit（W-v）小鼠中诱导的皮肤病变。PA注射导致Kit（W）/Kit（W-v）小鼠的皮肤病变比Kit（+/+）小鼠显著（> 2倍）大，Kit（+/+）小鼠在感染部位表现出明显的MC脱粒。此外，与Kit（+/+）小鼠相比，KitwlKitw-小鼠中PA注射后的中性粒细胞募集和感染部位的细菌清除显著受损。值得注意的是，在PA感染前将MC过继转移至Kit（W/）Kit（W-v）小鼠的皮肤导致正常的中性粒细胞积聚以及在细菌负荷和大小方面与Kit（+/+）小鼠相当的皮肤病变。这些发现首次证明，活化的MC对于诱导对细菌皮肤感染的保护性先天免疫应答至关重要。
Mast cells (MCs) have recently been shown to be essential for the elicitation of efficient immune responses in murine sepsis. To explore whether MCs also contribute to the control of bacterial skin infections, we studied skin lesions induced by Pseudomonas aeruginosa (PA) in genetically MC-deficient Kit(W)/Kit(W-v) mice, normal Kit(+/+) mice, and MC-reconstituted Kit(W)/Kit(W-v) mice. PA injections resulted in strikingly (> 2-fold) larger skin lesions in Kit(W)/Kit(W-v) mice than in Kit(+/+) mice, which exhibited pronounced MC degranulation at infection sites. In addition, neutrophil recruitment following PA injections and bacterial clearance from sites of infection was significantly impaired in KitwlKitw- mice compared with Kit(+/+) mice. Notably, the adoptive transfer of MCs to the skin of Kit(W/)Kit(W-v) mice before PA infection resulted in normal neutrophil accumulation as well as skin lesions comparable with those in Kit(+/+) mice in both bacterial burden and size. These findings demonstrate for the first time that activated MCs are crucial for the induction of protective innate immune responses to bacterial skin infections.