The Histoplasma capsulatum virulence factor CBP1 mediates a unique transcriptional signature associated with host-cell lysis
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ABSTRACT: keywords: murine bone marrow-derived macrophages response to Histoplasma capsulatum yeast infection In order to gain a better understanding of the macrophage response to infection with H. capsulatum, an intracellular fungal pathogen, we conducted a microarray timecourse analysis of gene expression in bone marrow-derived macrophages infected with H. capsulatum yeasts. The H. capsulatum gene CBP1 is required for virulence in animals, and is also necessary for macrophage lysis. Cbp1 protein is secreted, thus we hypothesized that it may interfere with macrophage signaling and/or gene expression. To test this, we compared macrophage gene expression profiles following infection with wild-type or cbp1 mutant yeasts. Additionally, we infected with UV-treated yeasts, which are phagocytosed and quickly degraded in the macrophage. Immediately following infection with either live, UV-treated, or cbp1 mutant yeasts, we observed a canonical inflammatory response signature from 1-3 hpi. At later time points following infection, we observe upregulation of several genes, including the pseudo-kinase Tribbles homolog 3, that have been linked to stress response and cell death in other cell types. The expression of these genes is dependent on CBP1, suggesting that this infection regulon may cause or respond to the initiation of a lytic program.
ORGANISM(S): Mus musculus
PROVIDER: GSE23378 | GEO | 2010/10/01
SECONDARY ACCESSION(S): PRJNA131281
REPOSITORIES: GEO
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