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Series GSE150802 Query DataSets for GSE150802
Status Public on Sep 02, 2020
Title Intracellular Cryptococcus neoformans Disrupts the Transcriptome Profile of M1- and M2-Polarized Host Macrophages
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Macrophages serve as a first line of defense against infection with the facultative intracellular pathogen, Cryptococcus neoformans (Cn). However, the ability of these innate phagocytic cells to destroy ingested Cn is strongly influenced by polarization state with classically (M1) activated macrophages better able to control cryptococcal infections than alternatively (M2) activated cells. While earlier studies have demonstrated that intracellular Cn minimally affects the expression of M1 and M2 markers, the impact on the broader transcriptome associated with these states remains unclear. To investigate this, we used an in vitro cell culture model of intracellular infection together with RNA sequencing-based transcriptome profiling to measure the impact of Cn infection on gene expression in both polarization states. The gene expression profile of both M1 and M2 cells was extensively altered to become more like naive (M0) macrophages. Gene ontology analysis suggested that this involved changes in the activity of the Janus kinase-signal transducers and activators of transcription (JAK-STAT), p53, and nuclear factor-κB (NF-κB) pathways. Analyses of the principle polarization markers at the protein-level also revealed discrepancies between the RNA- and protein-level responses. In contrast to earlier studies, intracellular Cn was found to increase protein levels of the M1 marker iNos. In addition, we identified common gene expression changes that occurred post-Cn infection, independent of polarization state. This included upregulation of the transcriptional co-regulator Cited1, which was also apparent at the protein level. These changes constitute a transcriptional signature of macrophage Cn infection and provide new insights into how Cn impacts gene expression and the phenotype of host phagocytes.
 
Overall design Naïve macrophage (naïve, M0, overall control), M1-polarized mock-infected (M1 control), M1-polarized pathogen-infected, M2-polarized mock-infected (M2 control), M1-polarized pathogen-infected were compared in a pairwise manner. Samples were used in triplicate, but analyses supported removal of 1 replicate for all treatments except M2-polarized pathogen-infected
 
Contributor(s) Seipelt-Thiemann R, Nelson DE, McClelland E
Citation(s) 32857777
Submission date May 18, 2020
Last update date Sep 02, 2020
Contact name Rebecca L Seipelt-Thiemann
E-mail(s) rebecca.seipelt@mtsu.edu
Phone 6159048393
Organization name Middle Tennessee State University
Department Biology
Street address 1301 E Main St Box 60
City Murfreesboro
State/province TN
ZIP/Postal code 37132
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (15)
GSM4558973 M1-polarized, mock-infected - replicate 1
GSM4558974 M1-polarized, mock-infected - replicate 2
GSM4558975 M1-polarized, mock-infected - replicate 3
Relations
BioProject PRJNA633619
SRA SRP262214

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Supplementary file Size Download File type/resource
GSE150802_genes.sorted_by_fold.sig_star_drop4.txt.gz 58.2 Kb (ftp)(http) TXT
GSE150802_reorganizedMacrophage2019_20200511.xlsx 3.7 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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