Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA.
J Infect Dis. 2012 Jul 1;206(1):91-8. doi: 10.1093/infdis/jis310. Epub 2012 May 4.
Brucella spp. are intracellular bacteria that establish lifelong infections whose mechanisms of chronicity are poorly understood. Notably, B cells facilitate the establishment of the high infection plateau that persists for months.
We evaluated the contribution of murine B cells toward providing infection niches for Brucella by using flow cytometry and microscopy and by determining live bacterial counts associated with B cells both in vivo and in vitro.
Herein we demonstrate that immunoglobulin M and complement-opsonized Brucella abortus infects and survives inside primary murine B cells protected from bactericidal effects of gentamicin. The entry was dependent on microfilaments for internalization and subsequently brucellae reside in a late endosomal/lysosomal compartment. Throughout the infection, 10% of colony-forming units from infected mice was associated with B cells, and these cells transferred disease to naive hosts. Furthermore, Brucella-positive cells were positive for transforming growth factor (TGF) β1, and about 10% of such cells were B cells, similar to rates found for other intracellular pathogens that induce their hosts cells to produce TGF-β1.
To conclude, infected B cells contribute to chronic bacterial infections by providing an intracellular niche that may exert an immunoregulatory role. Although professional phagocytic cells harbor intracellular bacteria including Brucella, infection of lymphocytes by bacteria has not been previously appreciated.
布鲁氏菌属是一种胞内细菌,可引起终身感染,其慢性感染的机制尚不清楚。值得注意的是,B 细胞促进了布鲁氏菌高感染平台的建立,该平台可持续数月。
我们通过流式细胞术和显微镜评估了小鼠 B 细胞对布鲁氏菌提供感染小生境的贡献,并通过体内和体外确定与 B 细胞相关的活细菌计数来确定。
本文证明了免疫球蛋白 M 和补体调理的布鲁氏菌流产感染并在原代小鼠 B 细胞中存活,这些 B 细胞免受庆大霉素的杀菌作用的影响。进入依赖于微丝的内化,随后布鲁氏菌位于晚期内体/溶酶体隔室中。在整个感染过程中,来自感染小鼠的 10%的集落形成单位与 B 细胞相关,这些细胞将疾病转移给了未感染的宿主。此外,布鲁氏菌阳性细胞呈转化生长因子 (TGF)β1 阳性,约 10%的此类细胞为 B 细胞,与诱导宿主细胞产生 TGF-β1 的其他胞内病原体的比率相似。
总之,受感染的 B 细胞通过提供可能发挥免疫调节作用的细胞内小生境来促进慢性细菌感染。尽管包括布鲁氏菌在内的专业吞噬细胞可携带胞内细菌,但以前尚未认识到细菌感染淋巴细胞。