Bacillus anthracis' lethal toxin induces broad transcriptional responses in human peripheral monocytes.
Bacillus anthracis' lethal toxin induces broad transcriptional responses in human peripheral monocytes.
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DOI：
10.1186/1471-2172-13-33
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发表时间：
2012-07-02
期刊：
影响因子：
3
通讯作者：
Southwick FS
中科院分区：
文献类型：
--
作者：
Chauncey KM;Lopez MC;Sidhu G;Szarowicz SE;Baker HV;Quinn C;Southwick FS
Anthrax lethal toxin (LT), produced by the Gram-positive bacterium Bacillus anthracis, is a highly effective zinc dependent metalloprotease that cleaves the N-terminus of mitogen-activated protein kinase kinases (MAPKK or MEKs) and is known to play a role in impairing the host immune system during an inhalation anthrax infection. Here, we present the transcriptional responses of LT treated human monocytes in order to further elucidate the mechanisms of LT inhibition on the host immune system. Western Blot analysis demonstrated cleavage of endogenous MEK1 and MEK3 when human monocytes were treated with 500 ng/mL LT for four hours, proving their susceptibility to anthrax lethal toxin. Furthermore, staining with annexin V and propidium iodide revealed that LT treatment did not induce human peripheral monocyte apoptosis or necrosis. Using Affymetrix Human Genome U133 Plus 2.0 Arrays, we identified over 820 probe sets differentially regulated after LT treatment at the p <0.001 significance level, interrupting the normal transduction of over 60 known pathways. As expected, the MAPKK signaling pathway was most drastically affected by LT, but numerous genes outside the well-recognized pathways were also influenced by LT including the IL-18 signaling pathway, Toll-like receptor pathway and the IFN alpha signaling pathway. Multiple genes involved in actin regulation, signal transduction, transcriptional regulation and cytokine signaling were identified after treatment with anthrax LT. We conclude LT directly targets human peripheral monocytes and causes multiple aberrant gene responses that would be expected to be associated with defects in human monocyte’s normal signaling transduction pathways and function. This study provides further insights into the mechanisms associated with the host immune system collapse during an anthrax infection, and suggests that anthrax LT may have additional downstream targets outside the well-known MAPK pathway.
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影响因子：
6.4
作者：
Elkord, E;Williams, PE;Rowbottom, AW
通讯作者：
Rowbottom, AW
DOI：
10.1073/pnas.90.21.10198
发表时间：
1993-11-01
影响因子：
11.1
作者：
HANNA, PC;ACOSTA, D;COLLIER, RJ
通讯作者：
COLLIER, RJ
DOI：
10.1073/pnas.79.10.3162
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LEPPLA, SH
通讯作者：
LEPPLA, SH
影响因子：
5.4
作者：
Tuttle, DL;Harrison, JK;Goodenow, MM
通讯作者：
Goodenow, MM
影响因子：
20.3
作者：
Edovitsky, E;Lerner, I;Elkin, M
通讯作者：
Elkin, M