T cells from Programmed Death-1 deficient mice respond poorly to Mycobacterium tuberculosis infection

PLoS One. 2011 May 12;6(5):e19864. doi: 10.1371/journal.pone.0019864.


Background: Programmed Death-1 (PD-1; CD279) receptor molecule is widely believed to be a negative regulator predominantly expressed by exhausted/activated mouse T cells. Upon interaction with its ligands, PD-L1 and PD-L2, PD-1 inhibits activation of T cells and cytokine production, which has been documented in various viral and fungal infections as well as in vitro studies. Therefore, inhibition of T cell responses by PD-1 resulted in disease resistance in a variety of mouse infection models studied heretofore.

Methodology/principal findings: Here, we report that PD-1 deficient (PD-1(-/-)) mice infected with Mycobacterium tuberculosis (M. tb) H37Rv by the aerosol route have increased susceptibility as compared with their wild type littermates. Surprisingly, M. tb antigen-specific T cell proliferation was dramatically reduced in PD-1 deficient animals compared with wild-type littermates, and this was due to increased numbers of regulatory T cells (Tregs) and recruitment of mesenchymal stem cells. Furthermore, PD-1(-/-) mice exhibited decreases in the autophagy-induced LC3-B marker protein in macrophages.

Conclusions/significance: Our findings suggest that PD-1 does not play an inhibitory role during M. tb infection and instead promotes mycobacterial clearance in mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Autophagy
  • Cell Proliferation
  • Flow Cytometry
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology*
  • T-Lymphocytes / immunology*
  • Tuberculosis / immunology
  • Tuberculosis / microbiology*