Depletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium

Abstract

The programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway could affect antimicrobial immune responses by suppressing T cell activity. Several recent studies demonstrated that blocking of the PD-1/PD-L1 pathway exacerbated Mycobacterium tuberculosis infection. However, the effect of blocking this pathway in pulmonary Mycobacterium avium–intracellulare complex (MAC) infection is not fully understood. Wild-type, PD-1-deficient mice, and PD-L1-deficient mice were intranasally infected with Mycobacterium avium bacteria. Depletion of PD-1 or PD-L1 did not affect mortality and bacterial burden in MAC-infected mice. However, marked infiltration of CD8-positive 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-positive T cells and related chemokine activity were upregulated in the infected lungs of PD-1 and PD-L1-deficient mice. Thus, the lack of change in susceptibility to MAC infection in PD-1 and PD-L1-deficient mice might be explained by the absence of obvious changes in the Th1 immune response. Furthermore, activated CD8-positive cells in response to MAC infection in these mice seemed to not be relevant in the control of MAC infection.

Virulence of Mycobacterium intracellulare clinical strains in a mouse model of lung infection – Role of neutrophilic inflammation in disease severity

“…A recent study showed that PD-1 plays a protective role in the host by suppressing over-production of IFN-γ by Th1 cells 31 . Moreover, deletion of PD-1 and/or PD-L1 did not affect the growth of M. avium subspecies hominissuis in mice 32 . CD4 + CD25 + regulatory T cells (Treg) are also considered to confer immunological tolerance because they express the transcription factor Foxp3, resulting in the suppression of IFN-γ and IL-2 production 33 .…”

Virulence of Mycobacterium intracellulare clinical strains in a mouse model of lung infection – role of neutrophilic inflammation in disease severity

“…A recent study showed that PD-1 plays a protective role in the host by suppressing over-production of IFN-γ by Th1 cells [ 33 ]. Moreover, deletion of PD-1 and/or PD-L1 did not affect the growth of M. avium subspecies hominissuis in mice [ 34 ]. CD4 + CD25 + regulatory T cells (Treg) are also considered to confer immunological tolerance because they express the transcription factor Foxp3, resulting in the suppression of IFN-γ and IL-2 production [ 35 ].…”