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Reverse-Phase Microarray Analysis Reveals Novel Targets in Lymph Nodes of Bacillus anthracis Spore-Challenged Mice

Show simple item record Popova, Taissia G. Espina, Virginia Liotta, Lance Popov, Serguei G. 2016-08-09T00:22:07Z 2016-08-09T00:22:07Z 2015-06-19
dc.identifier.citation Popova TG, Espina V, Liotta LA, Popov SG (2015) Reverse-Phase Microarray Analysis Reveals Novel Targets in Lymph Nodes of Bacillus anthracis Spore-Challenged Mice. PLoS ONE 10(6): e0129860. doi:10.1371/journal.pone.0129860 en_US
dc.description.abstract Anthrax is a frequently fatal infection of many animal species and men. The causative agent Bacillus anthracis propagates through the lymphatic system of the infected host; however, the specific interactions of the host and microbe within the lymphatics are incompletely understood. We report the first description of the phosphoprotein signaling in the lymph nodes of DBA/2 mice using a novel technique combining the reverse-phase microarray with the laser capture microdissesction. Mice were challenged into foot pads with spores of toxinogenic, unencapsulated Sterne strain. The spores quickly migrated to the regional popliteal lymph nodes and spread to the bloodstream as early as 3 h post challenge. All mice died before 72 h post challenge from the systemic disease accompanied by a widespread LN tissue damage by bacteria, including the hemorrhagic necrotizing lymphadenitis, infiltration of CD11b+ and CD3+ cells, and massive proliferation of bacteria in lymph nodes. A macrophage scavenger receptor CD68/macrosialin was upregulated and found in association with vegetative bacteria likely as a marker of their prior interaction with macrophages. The major signaling findings among the 65 tested proteins included the reduced MAPK signaling, upregulation of STAT transcriptional factors, and altered abundance of a number of pro- and anti-apoptotic proteins with signaling properties opposing each other. Downregulation of ERK1/2 was associated with the response of CD11b+ macrophages/dendritic cells, while upregulation of the pro-apoptotic Puma indicated a targeting of CD3+ T-cells. A robust upregulation of the anti-apoptotic survivin was unexpected because generally it is not observed in adult tissues. Taken together with the activation of STATs it may reflect a new pathogenic mechanism aimed to delay the onset of apoptosis. Our data emphasize a notion that the net biological outcome of disease is determined by a cumulative impact of factors representing the microbial insult and the protective capacity of the host.
dc.description.sponsorship This work was supported by the National Institutes of Health, USA, grant 5R21AI099851-2. Publication of this article was funded in part by the George Mason University Libraries Open Access Publishing Fund. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.subject Bacterial spores en_US
dc.subject Hematoxylin staining en_US
dc.subject Bacillus anthracis en_US
dc.subject Anthrax en_US
dc.subject Apoptosis en_US
dc.subject Bacterial pathogens en_US
dc.subject Phosphorylation en_US
dc.subject STAT signaling en_US
dc.title Reverse-Phase Microarray Analysis Reveals Novel Targets in Lymph Nodes of Bacillus anthracis Spore-Challenged Mice en_US
dc.type Article en_US

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