Butchar Jonathan P, Cremer Thomas J, Clay Corey D, Gavrilin Mikhail A, Wewers Mark D, Marsh Clay B, Schlesinger Larry S, Tridandapani Susheela
Division of Pulmonary and Critical Care, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
PLoS One. 2008 Aug 13;3(8):e2924. doi: 10.1371/journal.pone.0002924.
Francisella tularensis is a gram-negative facultative bacterium that causes the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. In order to help understand the mechanisms by which this occurs, we performed Affymetrix microarray analysis on transcripts from blood monocytes infected with the virulent Type A Schu S4 strain. Results showed that expression of several host response genes were reduced such as those associated with interferon signaling, Toll-like receptor signaling, autophagy and phagocytosis. When compared to microarrays from monocytes infected with the less virulent F. tularensis subsp. novicida, we found qualitative differences and also a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes in the Schu S4 strain. Notably, the PI3K/Akt1 pathway appeared specifically down-regulated following Schu S4 infection and a concomitantly lower cytokine response was observed. This study identifies several new factors potentially important in host cell subversion by the virulent Type A F. tularensis that may serve as novel targets for drug discovery.
土拉弗朗西斯菌是一种革兰氏阴性兼性细菌，即使接触少量细菌也会引发兔热病。弗朗西斯菌的一个关键特性是其抑制或破坏宿主免疫反应的能力。为了帮助理解这一过程发生的机制，我们对感染了强毒力A 型舒S4 菌株的血液单核细胞的转录本进行了Affymetrix 微阵列分析。结果显示，一些宿主反应基因的表达降低，例如那些与干扰素信号传导、Toll 样受体信号传导、自噬和吞噬作用相关的基因。与感染毒力较弱的土拉弗朗西斯菌新凶手亚种的单核细胞的微阵列相比，我们发现舒S4 菌株存在质量差异，并且促炎信号通路基因在数量上普遍呈现减少的模式。值得注意的是，PI3K/Akt1 通路在舒S4 感染后似乎特异性下调，并且观察到细胞因子反应相应降低。这项研究确定了几个在强毒力A 型土拉弗朗西斯菌破坏宿主细胞过程中可能重要的新因素，这些因素可能成为药物研发的新靶点。
