Siebenhaar Frank, Syska Wolfgang, Weller Karsten, Magerl Markus, Zuberbier Torsten, Metz Martin, Maurer Marcus
Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Am J Pathol. 2007 Jun;170(6):1910-6. doi: 10.2353/ajpath.2007.060770.
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 Kit(W)/Kit(W-v) 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.
肥大细胞(MCs)最近被证明对小鼠脓毒症中有效免疫反应的引发至关重要。为了探究MCs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)在基因MC缺陷的Kit(W)/Kit(W-v)小鼠、正常的Kit(+/+)小鼠以及MC重构的Kit(W)/Kit(W-v)小鼠中诱导的皮肤损伤。PA注射导致Kit(W)/Kit(W-v)小鼠的皮肤损伤比Kit(+/+)小鼠显著(>2倍)更大,后者在感染部位表现出明显的MC脱颗粒。此外,与Kit(+/+)小鼠相比,Kit(W)/Kit(W-v)小鼠在PA注射后中性粒细胞募集以及感染部位细菌清除均显著受损。值得注意的是,在PA感染前将MCs过继转移至Kit(W)/Kit(W-v)小鼠皮肤,导致中性粒细胞正常积累,且皮肤损伤在细菌负荷和大小方面均与Kit(+/+)小鼠相当。这些发现首次证明活化的MCs对于诱导针对细菌性皮肤感染的保护性固有免疫反应至关重要。