Host microarray analysis reveals a role for the Salmonella response regulator phoP in human macrophage cell death
Host microarray analysis reveals a role for the Salmonella response regulator phoP in human macrophage cell death
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DOI：
10.1073/pnas.091110098
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发表时间：
2001-05-08
影响因子：
11.1
通讯作者：
Falkow, S
中科院分区：
文献类型：
--
作者：
Detweiler, CS;Cunanan, DB;Falkow, S
细菌病原体操纵宿主细胞以促进病原体存活和传播。我们使用了22,571人cDNA微阵列，通过比较感染野生型细菌或phoP：：Tn 10突变株的人单核细胞组织培养细胞的表达谱，来识别受沙门氏菌鼠伤寒亚种phoP基因（毒力所需的转录因子）影响的宿主途径。野生型和phoP：：Tn 10细菌都诱导了一组共同的基因，其中许多是促炎基因。差异表达的基因包括那些影响宿主细胞死亡的基因，表明phoP调节系统控制改变巨噬细胞存活的细菌基因。随后的实验表明，phoP：：Tn 10突变株在杀死水浴培养的和原代人巨噬细胞方面有缺陷，但能够在细胞内复制。这些实验表明phoP在沙门氏菌诱导的人巨噬细胞死亡中起作用。
Bacterial pathogens manipulate host cells to promote pathogen survival and dissemination. We used a 22,571 human cDNA microarray to identify host pathways that are affected by the Salmonella enterica subspecies typhimurium phoP gene, a transcription factor required for virulence, by comparing the expression profiles of human monocytic tissue culture cells infected with either the wild-type bacteria or a phoP::Tn10 mutant strain. Both wild-type and phoP::Tn10 bacteria induced a common set of genes, many of which are proinflammatory. Differentially expressed genes included those that affect host cell death, suggesting that the phoP regulatory system controls bacterial genes that alter macrophage survival, Subsequent experiments showed that the phoP::Tn10 mutant strain is defective for killing bath cultured and primary human macrophages but is able to replicate intracellularly. These experiments indicate that phoP plays a role in Salmonella-induced human macrophage cell death.