GSE169202
Gene signature profiles in lung tisses of wild type mice or PD-1 or PD-L1 deficient mice  infected with Mycobacterium avium
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.