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Series GSE169202 Query DataSets for GSE169202
Status Public on Sep 15, 2021
Title Gene signature profiles in lung tisses of wild type mice or PD-1 or PD-L1 deficient mice infected with Mycobacterium avium
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Rationale: T cell activation is a key antimicrobial component against mycobacterial disease. Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway could affect the antimicrobial immune responses by suppressing T cell activity. Several recent studies demonstrated that blocking of PD-1/PD-L1 pathway exacerbated Mycobacterium tuberculosis infection. However, the influence of blocking this pathway in pulmonary Mycobacterium avium-intracellulare complex (MAC) infection was not fully understood. Objective: We aimed to determine the influence of genetic depletion of PD-1/PD-L1 pathway on the disease activity of MAC infection. Methods: Wild-type, PD-1-deficient mice and PD-L1-deficient mice were intranasally infected with Mycobacterium avium bacteria. Measurements and Main Results: The depletion of PD-1 or PD-L1 did not affect mortality and bacterial burden in mice infected with MAC. However, remarkable infiltration of CD8 T lymphocytes was observed in the lungs of PD-1 and PD-L1 deficient mice compared to wild-type mice. Comprehensive transcriptome analysis showed that levels of gene expressions related to Th1 immunity did not differ according to the genotypes. However, genes related to the activity of CD8 T cells and related chemokine activity were up-regulated in the infected lungs of PD-1 and PD-L1 deficient mice. Conclusions: Depletion of PD-1/PD-L1 pathway did not affect the activation of Th1 immunity in response to MAC infection, which may explain why MAC infection was controlled in these mice. In addition, CD8-positive T cell pulmonary inflammation in knockout mice might have some clinical implication in the treatment of cancer patients with immune checkpoint inhibitors when the patients are infected with MAC.
Overall design 18 strand-specific RNA libraries for high-throughput sequencing were prepared (3 from the lungs of the wild type mice treated with saline, 3 from the lungs of the PD-1-/- mice treated with saline, 3 from the lungs of the PD-L1-/- mice treated with saline,3 from the lungs of the wild type mice infected with M. avium for 2 months, 3 from the lungs of the PD-1-/- mice infected with M. avium for 2 months, and 3 from the lungs of the PD-L1-/- mice infected with M. avium for 2 months) using the Illumina Stranded mRNA Sample Preparation Kit with 500ng of total RNA according to manufacturer’s instructions.
Contributor(s) Matsuyama M, Nakajima M, Muratani M, Hizawa N
Citation(s) 34504192
Submission date Mar 19, 2021
Last update date Sep 15, 2021
Contact name Masashi Matsuyama
Organization name Tsukuba university
Department respiratory medicine
Street address 1-1-1 AMAKUBO
State/province IBARAKI
ZIP/Postal code 305-8575
Country Japan
Platforms (1)
GPL9185 Illumina Genome Analyzer (Mus musculus)
Samples (18)
GSM5183414 Wildtype mice control 1
GSM5183415 Wildtype mice control 2
GSM5183416 Wildtype mice control 3
BioProject PRJNA715641
SRA SRP311328

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Supplementary file Size Download File type/resource
GSE169202_PD-1_visualized_data.xlsx 17.1 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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