title: Kallistatin modulates immune cells and confers anti-inflammatory response to protect mice from group A streptococcal infection.
abstract: 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 1β, 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.
authors: Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
authors: Shiou-Ling
authors: SL
authors: Lu
authors: Chiau-Yuang
authors: CY
authors: Tsai
authors: Yueh-Hsia
authors: YH
authors: Luo
authors: Chih-Feng
authors: CF
authors: Kuo
authors: Wei-Chieh
authors: WC
authors: Lin
authors: Yu-Tzu
authors: YT
authors: Chang
authors: Jiunn-Jong
authors: JJ
authors: Wu
authors: Woei-Jer
authors: WJ
authors: Chuang
authors: Ching-Chuan
authors: CC
authors: Liu
authors: Lee
authors: L
authors: Chao
authors: Julie
authors: J
authors: Chao
authors: Yee-Shin
authors: YS
authors: Lin
mesh_terms: D000818:Animals; D015870:Gene Expression; D006801:Humans; D056747:Immunomodulation; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D015843:Serpins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000472:pathogenicity; D016019:Survival Analysis; D019076:Transgenes; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000093242:Interleukin-6 Inhibitors
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D015843:Serpins; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C051324:kallistatin
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