Junqueira-Kipnis Ana Paula, Kipnis Andre, Henao Tamayo Marcela, Harton Marisa, Gonzalez Juarrero Mercedes, Basaraba Randall J, Orme Ian M
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins 80523, USA.
Immunology. 2005 Jun;115(2):246-52. doi: 10.1111/j.1365-2567.2005.02136.x.
Mice on the CBA inbred strain background expressing the well characterized mutation designated xid in the cytoplasmic signalling enzyme Bruton's protein kinase have been previously noted to illustrate shifts in T helper type 1 (Th1)/Th2 immunity which is underlined by an apparent failure to produce the regulatory cytokine interleukin-10. In the current study we examined if this extended to infection with Mycobacterium tuberculosis, which also depends on Th1 immunity. Contrary to expectations, xid mice showed evidence of a transient early susceptibility to pulmonary infection, changes in macrophage morphology, and decreased activation of lung natural killer cells, while showing evidence of substantial IL-10 production and accumulation in lung lesions macrophages, but paradoxically this did not influence the course of the chronic disease. In addition, macrophages from the lungs of xid mice also expressed high levels of CD14. These observations suggest that the xid mutation in cellular signalling has much wider effects on the immune system than previously thought.
在细胞质信号酶布鲁顿蛋白激酶中表达特征明确的xid突变的CBA近交系背景小鼠，此前已被注意到表现出1型辅助性T细胞（Th1）/Th2免疫的转变，这表现为明显无法产生调节性细胞因子白细胞介素-10。在本研究中，我们研究了这种情况是否也适用于结核分枝杆菌感染，结核分枝杆菌感染同样依赖于Th1免疫。与预期相反，xid小鼠表现出对肺部感染短暂早期易感性的证据、巨噬细胞形态的变化以及肺自然杀伤细胞激活的降低，同时显示出在肺部病变巨噬细胞中有大量白细胞介素-10产生和积累的证据，但矛盾的是，这并未影响慢性病的病程。此外，xid小鼠肺部的巨噬细胞也表达高水平的CD14。这些观察结果表明，细胞信号传导中的xid突变对免疫系统的影响比之前认为的要广泛得多。
