Tam Stanley, Maksaereekul Saipiroon, Hyde Dallas M, Godinez Ivan, Beaman Blaine L
Respiratory Disease Unit, California National Primate Research Center (CNPRC), University of California, Davis, CA 95616, USA.
Microbes Infect. 2012 Nov;14(13):1133-43. doi: 10.1016/j.micinf.2012.05.008. Epub 2012 May 23.
The early host response during pulmonary nocardiosis is highly dependent on neutrophils and the successful clearance of bacteria in tissue. The data presented in this study showed that IL-17 mediated the neutrophil response following intranasal inoculation with Nocardia asteroides strain GUH-2. Flow cytometry revealed that neutrophil levels in C57BL/6 mice were increased by day 1 post inoculation and remained elevated until day 3, during which time the majority of bacterial clearance occurred. Intracellular cytokine staining for IL-17 showed a 3.5- to 5-fold increase in IL-17 producing T-lymphocytes that were predominately comprised by CD4(-)CD8(-) γδ T-lymphocytes. The importance of IL-17 and γδ T-cells was determined by the in vivo administration of antibody, capable of blocking IL-17 binding or TCR δ, respectively. Neutralization of either IL-17 or γδ T-cells in Nocardia treated mice resulted in attenuated neutrophil infiltration. Paralleling this impaired neutrophil recruitment, nearly a 10-fold increase in bacterial burden was observed in both anti-IL-17 and anti-TCR δ treated animals. Together, these data indicate a protective role for IL-17 and suggest that IL-17 producing γδ T-lymphocytes contribute to neutrophil infiltration during pulmonary nocardiosis.
肺诺卡菌病早期的宿主反应高度依赖中性粒细胞以及组织中细菌的成功清除。本研究呈现的数据表明，白细胞介素-17（IL-17）介导了鼻内接种星形诺卡菌GUH-2菌株后的中性粒细胞反应。流式细胞术显示，C57BL/6小鼠接种后第1天中性粒细胞水平升高，并持续升高至第3天，在此期间大部分细菌被清除。对IL-17进行细胞内细胞因子染色显示，产生IL-17的T淋巴细胞增加了3.5至5倍，这些细胞主要由CD4(-)CD8(-)γδT淋巴细胞组成。通过体内分别给予能够阻断IL-17结合或TCRδ的抗体来确定IL-17和γδT细胞的重要性。在诺卡菌处理的小鼠中，中和IL-17或γδT细胞均导致中性粒细胞浸润减弱。与这种中性粒细胞募集受损情况平行的是，在抗IL-17和抗TCRδ处理的动物中均观察到细菌负荷增加了近10倍。总之，这些数据表明IL-17具有保护作用，并提示产生IL-17的γδT淋巴细胞在肺诺卡菌病期间有助于中性粒细胞浸润。
