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Series GSE113054 Query DataSets for GSE113054
Status Public on May 09, 2018
Title Bhlhe40 is an essential repressor of IL-10 during Mycobacterium tuberculosis infection
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The cytokine IL-10 antagonizes pathways that control Mycobacterium tuberculosis (Mtb) infection. Nevertheless, the impact of IL-10 during Mtb infection has been difficult to decipher because loss of function studies in animal models have yielded only mild phenotypes. We have discovered that the transcription factor Bhlhe40 is required to repress Il10 expression during Mtb infection. Loss of Bhlhe40 in mice results in higher Il10 expression, higher bacterial burden, and early susceptibility similar to that observed in mice lacking IFN-g. Deletion of Il10 in Bhlhe40-/- mice reverses these phenotypes. Bhlhe40 deletion in T cells or CD11c+ cells is sufficient to cause susceptibility to Mtb. Bhlhe40 represents the first transcription factor found to be essential during Mtb infection to specifically regulate Il10 expression, revealing the importance of strict control of IL-10 production by innate and adaptive immune cells during infection. Our findings uncover a previously elusive but significant role for IL-10 in Mtb pathogenesis.
Overall design Bhlhe40+/+ and Bhlhe40-/- GM-CSF-cultured bone marrow-derived cells were stimulated in the presence of 10 µg/ml heat-killed Mycobacterium tuberculosis (H37Ra strain, Difco) for 4 hours. Bhlhe40+/+ and Bhlhe40-/- in vitro-polarized TH1 cells were stimulated with PMA (50 ng/ml, Enzo Life Sciences) and ionomycin (1 µM, Enzo Life Sciences) for 1.5 hours. After stimulation, cells were fixed and genomic DNA was immunoprecipitated with anti-Bhlhe40 antibody.
Contributor(s) Huynh JP, Lin C, Kimmey JM, Jarjour NN, Schwarkopf EA, Bradstreet TR, Shchukina I, Shpynov O, Weaver CT, Taneja R, Artyomov MN, Edelson BT, Stalling CL
Citation(s) 29773644
Submission date Apr 12, 2018
Last update date Feb 11, 2019
Contact name Maxim Artyomov
Organization name Washington University in St. Louis
Department Pathology and Immunology
Lab Artyomov Lab
Street address 425 S Euclid Ave
City St. Louis
State/province MO
ZIP/Postal code 63110
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (4)
GSM3094813 Bhlhe40_WT_GM_ChIPseq
GSM3094814 Bhlhe40_KO_GM_ChIPseq
GSM3094815 Bhlhe40_WT_Th1_ChIPseq
BioProject PRJNA449905
SRA SRP139778

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Supplementary file Size Download File type/resource
GSE113054_RAW.tar 347.1 Mb (http)(custom) TAR (of BW)
GSE113054_gm_annotated_peaks.txt.gz 16.6 Kb (ftp)(http) TXT
GSE113054_th1_annotated_peaks.txt.gz 228.3 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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