Department of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China.
Department of Radiation Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Infect Dis. 2018 Jun 5;218(1):64-74. doi: 10.1093/infdis/jiy149.
Mast cells (MCs) play a key role in immune process response to invading pathogens.
This study assessed the involvement of MCs in controlling Staphylococcus aureus infection in a cutaneous infection model of MC-deficient (KitW-sh/W-sh) mice.
KitW-sh/W-sh mice developed significantly larger skin lesions after the cutaneous S. aureus challenge, when compared to wild-type (WT) mice, while MC dysfunction reduced the inflammation response to S. aureus. The levels of tumor necrosis factor (TNF)-α in skin tissues were significantly decreased in KitW-sh/W-sh mice upon infection. Moreover, the exogenous administration of MCs or recombinant TNF-α effectively restored the immune response against S. aureus in KitW-sh/W-sh mice via the recruitment of neutrophils to the infected site. These results indicate that the effects of MC deficiency are largely attributed to the decrease in production of TNF-α in cutaneous S. aureus infection. In addition, S. aureus-induced MC activation was dependent on the c-kit receptor-activated phosphoinositide 3-kinase (PI3K)/AKT/P65-nuclear factor (NF-κB) pathway, which was confirmed by treatment with Masitinib (a c-kit receptor inhibitor), Wortmannin (a PI3K inhibitor), and pyrrolidine dithiocarbamate (a NF-κB inhibitor), respectively.
The present study identifies the critical role of MCs in the host defense against S. aureus infection.
肥大细胞（MCs）在免疫过程中对入侵病原体的反应中起着关键作用。
本研究评估了 MCs 在控制皮肤金黄色葡萄球菌感染模型中 MC 缺陷（KitW-sh/W-sh）小鼠感染中的作用。
与野生型（WT）小鼠相比，KitW-sh/W-sh 小鼠在皮肤金黄色葡萄球菌挑战后皮肤损伤明显更大，而 MC 功能障碍会降低金黄色葡萄球菌的炎症反应。感染后，KitW-sh/W-sh 小鼠皮肤组织中的肿瘤坏死因子（TNF）-α水平显著降低。此外，通过将中性粒细胞募集到感染部位，MC 或重组 TNF-α的外源性给药可有效恢复 KitW-sh/W-sh 小鼠对金黄色葡萄球菌的免疫反应。这些结果表明，MC 缺乏的影响主要归因于皮肤金黄色葡萄球菌感染中 TNF-α产生的减少。此外，金黄色葡萄球菌诱导的 MC 激活依赖于 c-kit 受体激活的磷酸肌醇 3-激酶（PI3K）/AKT/P65-核因子（NF-κB）途径，这分别通过 Masitinib（c-kit 受体抑制剂）、Wortmannin（PI3K 抑制剂）和吡咯烷二硫代氨基甲酸盐（NF-κB 抑制剂）的处理得到证实。
本研究确定了 MCs 在宿主防御金黄色葡萄球菌感染中的关键作用。
