Murakami Tesshin, Hatano Shinya, Yamada Hisakata, Iwakura Yoichiro, Yoshikai Yasunobu
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka.
Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan.
J Infect Dis. 2016 Dec 1;214(11):1752-1761. doi: 10.1093/infdis/jiw443. Epub 2016 Sep 20.
Klebsiella pneumoniae frequently causes life-threatening infection in children. Interleukin 17A (IL-17A) is known to be involved in protection against K. pneumoniae infection through activation of neutrophils.
We found that IL-17A-producing γδ T cells existed more frequently in younger mice on examination of IL-17A-producing lymphocytes in the lung of naive mice at various ages. We hence compared the protective role of IL-17A-producing γδ T cells against pulmonary K. pneumoniae infection in young (3 weeks old) and adult (8-12 weeks old) mice. IL-17A-deficient mice were susceptible to K. pneumonia regardless of age. Cγ-, Vγ4/6-, or Vδ1-deficient mice were susceptible to K. pneumonia at young age, while interleukin 23p19 (IL-23p19)-deficient mice were susceptible at adult age. IL-17A-producing Vγ1Vγ4 γδ T cells expressing canonical Vγ6/Vδ1 genes were dominant over IL-17A-producing Vγ4 γδ T cells in the lungs of young mice after infection. The IL-17A-producing Vγ1Vγ4 γδ T cells expressed an activation marker, CD69, and proliferated in an IL-23-independent manner, while the IL-17A-producing Vγ4 γδ T cells expressing IL-23 receptor but no CD69 proliferated in IL-23-dependent manner.
These results suggest that 2 types of IL-17A-producing γδ T cells are activated for host defense against K. pneumoniae infection by IL-23-dependent or independent mechanism.
肺炎克雷伯菌经常在儿童中引起危及生命的感染。已知白细胞介素17A(IL-17A)通过激活中性粒细胞参与抵御肺炎克雷伯菌感染。
我们在检查不同年龄的未感染小鼠肺中产生IL-17A的淋巴细胞时发现,产生IL-17A的γδT细胞在年幼小鼠中更为常见。因此,我们比较了产生IL-17A的γδT细胞对幼年(3周龄)和成年(8 - 12周龄)小鼠肺部肺炎克雷伯菌感染的保护作用。IL-17A缺陷小鼠无论年龄大小都易感染肺炎克雷伯菌。Cγ、Vγ4/6或Vδ1缺陷小鼠在幼年时易感染肺炎克雷伯菌,而白细胞介素23p19(IL-23p19)缺陷小鼠在成年时易感染。感染后,在幼年小鼠肺中,表达典型Vγ6/Vδ1基因的产生IL-17A的Vγ1Vγ4γδT细胞比产生IL-17A的Vγ4γδT细胞占优势。产生IL-17A的Vγ1Vγ4γδT细胞表达激活标志物CD69,并以不依赖IL-23的方式增殖,而表达IL-23受体但不表达CD69的产生IL-17A的Vγ4γδT细胞以依赖IL-23的方式增殖。
这些结果表明,两种类型的产生IL-17A的γδT细胞通过依赖IL-23或不依赖IL-23的机制被激活,以抵御肺炎克雷伯菌感染,保护宿主。