Kallistatin modulates immune cells and confers anti-inflammatory response to protect mice from group a streptococcal infection

Shiou Ling Lu, Chiau Yuang Tsai, Yueh Hsia Luo, Chih Feng Kuo, Wei Chieh Lin, Yu Tzu Chang, Jiunn Jong Wu, Woei Jer Chuang, Ching Chuan Liu, Lee Chao, Julie Chao, Yee Shin Lin

研究成果: 雜誌貢獻期刊論文同行評審

33 引文 斯高帕斯(Scopus)


Group A streptococcus (GAS) infection may cause severe life-threatening diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Despite the availability of effective antimicrobial agents, there has been a worldwide increase in the incidence of invasive GAS infection. Kallistatin (KS), originally found to be a tissue kallikrein-binding protein, has recently been shown to possess anti-inflammatory properties. However, its efficacy in microbial infection has not been explored. In this study, we transiently expressed the human KS gene by hydrodynamic injection and investigated its anti-inflammatory and protective effects in mice via air pouch inoculation of GAS. The results showed that KS significantly increased the survival rate of GAS-infected mice. KS treatment reduced local skin damage and bacterial counts compared with those in mice infected with GAS and treated with a control plasmid or saline. While there was a decrease in immune cell infiltration of the local infection site, cell viability and antimicrobial factors such as reactive oxygen species actually increased after KS treatment. The efficiency of intracellular bacterial killing in neutrophils was directly enhanced by KS administration. Several inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1, and interleukin 6, in local infection sites were reduced by KS. In addition, KS treatment reduced vessel leakage, bacteremia, and liver damage after local infection. Therefore, our study demonstrates that KS provides protection in GAS-infected mice by enhancing bacterial clearance, as well as reducing inflammatory responses and organ damage.

頁(從 - 到)5366-5372
期刊Antimicrobial Agents and Chemotherapy
出版狀態已出版 - 11月 2013


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