Pei Jianwu, Turse Joshua E, Ficht Thomas A
Department of Veterinary Pathobiology, Texas A&M University and Texas Agricultural Experiment Station, College Station, TX 77843-4467, USA.
Microbes Infect. 2008 May;10(6):582-90. doi: 10.1016/j.micinf.2008.01.005. Epub 2008 Jan 20.
Smooth Brucella abortus S2308 is virulent while rough derivatives are attenuated. Intracellular killing is often blamed for these differences. In the studies described, uptake kinetics and interaction of S2308 and S2308 manBA::Tn5 (CA180) rough mutants with macrophages were investigated. The results revealed that smooth B. abortus was rapidly internalized, achieving a maximum level in less than 5 min without additional uptake over the next 30 min. In contrast, continued uptake of the rough mutant was observed and only achieves a maximum level after 30 min. The results were confirmed by the differences in F-actin polymerization, lipid raft staining, early endosome colocalization and electron microscopic observations after smooth and rough Brucella infection. We also demonstrated for the first time that uptake of S2308, but not rough mutant CA180 was PI3-kinase and toll-like receptor 4 (TLR4) dependent. Differences in uptake were associated with differences in macrophage activation with regard to NF-kappaB translocation and cytokine production. These results provide evidence that the presence of B. abortus OPS dictates the interactions between Brucella and specific cell surface receptors minimizing macrophage activation and enhancing Brucella survival and/or persistence.
光滑型布鲁氏菌流产株S2308具有毒力，而粗糙型衍生物则减毒。细胞内杀伤作用常被认为是造成这些差异的原因。在所述研究中，研究了S2308和S2308 manBA::Tn5（CA180）粗糙型突变体与巨噬细胞的摄取动力学及相互作用。结果显示，光滑型流产布鲁氏菌迅速被内化，在不到5分钟内达到最高水平，在接下来的30分钟内没有额外摄取。相比之下，观察到粗糙型突变体持续摄取，且仅在30分钟后达到最高水平。光滑型和粗糙型布鲁氏菌感染后，F-肌动蛋白聚合、脂筏染色、早期内体共定位及电子显微镜观察的差异证实了这些结果。我们还首次证明，S2308的摄取，但粗糙型突变体CA180的摄取不依赖于PI3激酶和Toll样受体4（TLR4）。摄取差异与巨噬细胞在NF-κB易位和细胞因子产生方面的激活差异有关。这些结果提供了证据，表明流产布鲁氏菌OPS的存在决定了布鲁氏菌与特定细胞表面受体之间的相互作用，从而使巨噬细胞激活最小化，并增强布鲁氏菌的存活和/或持久性。
