TY - JOUR
T1 - Transcriptional profiling of murine organ genes in response to infection with Bacillus anthracis Ames spores
AU - Moen, Scott T.
AU - Yeager, Linsey A.
AU - Lawrence, William S.
AU - Ponce, Cindy
AU - Galindo, Cristi L.
AU - Garner, Harold R.
AU - Baze, Wallace B.
AU - Suarez, Giovanni
AU - Peterson, Johnny
AU - Chopra, Ashok K.
N1 - Funding Information:
This research was supported by the US Army Grant (DAMD 170210699), the NIH (U01 AI 5385802 and N01 AI 30065), and NIH/NIAID Western Regional Center of Excellence 1U54 AI057156-01. Cristi L. Galindo received support from an NIH cardiology fellowship, Cardiology Department, University of Texas Southwestern Medical Center. We would like to thank Dr. T. Wood and his staff from the Department of Biochemistry and Molecular Biology at UTMB for providing facility of his core laboratory for microarray studies.
PY - 2008/4
Y1 - 2008/4
N2 - Bacillus anthracis is the Gram-positive, spore-forming etiological agent of anthrax, an affliction studied because of its importance as a potential bioweapon. Although in vitro transcriptional responses of macrophages to either spore or anthrax toxins have been previously reported, little is known regarding the impact of infection on gene expression in host tissues. We infected Swiss-Webster mice intranasally with 5 LD50 of B. anthracis-virulent Ames spores and observed the global transcriptional profiles of various tissues over a 48 h time period. RNA was extracted from spleen, lung, and heart tissues of infected and control mice and examined by Affymetrix GeneChip analysis. Approximately 580 host genes were significantly over or under expressed among the lung, spleen, and heart tissues at 8 and 48 h time points. Expression of genes encoding for surfactant and major histocompatibility complex (MHC) presentation was diminished during the early phase of infection in lungs. By 48 h, a significant number of genes were modulated in the heart, including up-regulation of calcium-binding-related gene expression, and down-regulation of multiple genes related to cell adhesion, formation of the extracellular matrix, and the cell cytoskeleton. Interestingly, the spleen 8 h post-infection showed striking increases in the expression of genes that encode hydrolytic enzymes, and these levels remained elevated throughout infection. Further, genes involving antigen presentation and interferon responses were down-regulated in the spleen at 8 h. In late stages of infection, splenic genes related to the inflammatory response were up-regulated. This study is the first to describe the in vivo global transcriptional response of multiple organs during inhalational anthrax. Although numerous genes related to the host immunological response and certain protection mechanisms were up-regulated in these organs, a vast list of genes important for fully developing and maintaining this response were decreased. Additionally, the lung, spleen, and heart showed differential responses to the infection, further validating the demand for a better understanding of anthrax pathogenesis in order to design therapies against novel targets.
AB - Bacillus anthracis is the Gram-positive, spore-forming etiological agent of anthrax, an affliction studied because of its importance as a potential bioweapon. Although in vitro transcriptional responses of macrophages to either spore or anthrax toxins have been previously reported, little is known regarding the impact of infection on gene expression in host tissues. We infected Swiss-Webster mice intranasally with 5 LD50 of B. anthracis-virulent Ames spores and observed the global transcriptional profiles of various tissues over a 48 h time period. RNA was extracted from spleen, lung, and heart tissues of infected and control mice and examined by Affymetrix GeneChip analysis. Approximately 580 host genes were significantly over or under expressed among the lung, spleen, and heart tissues at 8 and 48 h time points. Expression of genes encoding for surfactant and major histocompatibility complex (MHC) presentation was diminished during the early phase of infection in lungs. By 48 h, a significant number of genes were modulated in the heart, including up-regulation of calcium-binding-related gene expression, and down-regulation of multiple genes related to cell adhesion, formation of the extracellular matrix, and the cell cytoskeleton. Interestingly, the spleen 8 h post-infection showed striking increases in the expression of genes that encode hydrolytic enzymes, and these levels remained elevated throughout infection. Further, genes involving antigen presentation and interferon responses were down-regulated in the spleen at 8 h. In late stages of infection, splenic genes related to the inflammatory response were up-regulated. This study is the first to describe the in vivo global transcriptional response of multiple organs during inhalational anthrax. Although numerous genes related to the host immunological response and certain protection mechanisms were up-regulated in these organs, a vast list of genes important for fully developing and maintaining this response were decreased. Additionally, the lung, spleen, and heart showed differential responses to the infection, further validating the demand for a better understanding of anthrax pathogenesis in order to design therapies against novel targets.
KW - Affymetrix microarrays
KW - Anthrax
KW - Bacillus anthracis
KW - Murine model of infection
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U2 - 10.1016/j.micpath.2007.10.004
DO - 10.1016/j.micpath.2007.10.004
M3 - Article
C2 - 18037264
AN - SCOPUS:40749155312
SN - 0882-4010
VL - 44
SP - 293
EP - 310
JO - Microbial Pathogenesis
JF - Microbial Pathogenesis
IS - 4
ER -