Brucella melitensis, B. neotomae and B. ovis elicit common and distinctive macrophage defense transcriptional responses.
Brucella melitensis, B. neotomae and B. ovis elicit common and distinctive macrophage defense transcriptional responses.
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DOI：
10.3181/0904-rm-124
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发表时间：
2009-12
期刊：
影响因子：
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通讯作者：
Splitter G
中科院分区：
文献类型：
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作者：
Covert J;Mathison AJ;Eskra L;Banai M;Splitter G
布鲁氏菌属在巨噬细胞中建立一个细胞内复制的生态位，而巨噬细胞试图通过天然的防御机制来消灭细菌。布鲁氏菌属拥有相似的基因组，但表现出不同的巨噬细胞感染。在4-8小时内发生细胞内适应的情况下，很少有山羊和新瘤巴氏杆菌进入巨噬细胞。相反，绵羊分枝杆菌很容易被巨噬细胞吞噬，并表现出持续的感染平台。评价早期巨噬细胞与布鲁氏菌的相互作用。允许发现宿主进入和细胞内转位机制。不同布鲁氏菌感染4小时后巨噬细胞转录反应的微阵列分析。发现与未感染的巨噬细胞相比，普通巨噬细胞的基因表达发生了变化。三种不同的布鲁氏菌感染巨噬细胞。引发一种常见的先天性免疫主题，增加趋化因子和防御反应基因的转录水平，降低GTPase信号和细胞骨架功能的转录水平，这可能会影响含有布鲁氏菌的囊泡的运输。例如，与趋化相关基因(IL-1β、MIP-1α)、细胞因子调节(SOCS3)和防御相关基因(Fas、肿瘤坏死因子)的转录水平升高，而与囊泡运输相关的基因(Rab3d)和溶酶体相关酶(丙皂蛋白)的转录水平下降。布鲁氏菌中巨噬细胞转录水平改变的基因。感染可能与物种特定的宿主防御和细胞内生存策略有关。根据感染布鲁氏菌的种类，基因本体论分类确定了与细胞生长和维持、内肽酶抑制活性和G蛋白介导的信号转导有关的不同基因。在羊种布鲁氏菌感染中基因表达降低的例子，但在其他布鲁氏菌中没有。生长停滞(Gas2)、免疫球蛋白受体(Fcγri)和趋化因子受体(CXCR4)基因，提示对细胞内功能的相反作用。
Brucella spp. establish an intracellular replicative niche in macrophages, while macrophages attempt to eliminate the bacteria by innate defense mechanisms. Brucella spp. possess similar genomes yet exhibit different macrophage infections. Few B. melitensis and B. neotomae enter macrophages with intracellular adaptation occurring over 4–8 hr. Conversely, B. ovis are readily ingested by macrophages and exhibit a persistent plateau of infection. Evaluating early macrophage interaction with Brucella spp. allows discovery of host entry and intracellular translocation mechanisms. Microarray analysis of macrophage transcriptional response following a 4 hr infection by different Brucella spp. revealed common macrophage genes altered in expression compared to uninfected macrophages. Macrophage infection with three different Brucella spp. provokes a common innate immune theme with increased transcript levels of chemokines and defense response genes and decreased transcript levels of GTPase signaling and cytoskeletal function that may affect trafficking of Brucella containing vesicles. For example, transcript levels of genes associated with chemotaxis (IL-1β, MIP-1α), cytokine regulation (Socs3) and defense (Fas, Tnf) were increased, while transcript levels of genes associated with vesicular trafficking (Rab3d) and lysosomal associated enzymes (prosaposin) were decreased. Genes with altered macrophage transcript levels among Brucella spp. infections may correlate with species specific host defenses and intracellular survival strategies. Depending on the infecting Brucella species, gene ontology categorization identified genes differentially involved in cell growth and maintenance, endopeptidase inhibitor activity and G-protein mediated signaling. Examples of decreased gene expression in B. melitensis infection but not other Brucella spp. were growth arrest (Gas2), immunoglobulin receptor (FcγrI) and chemokine receptor (Cxcr4) genes, suggesting opposing effects on intracellular functions.