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

Tousif S, Singh Y, Prasad DV, Sharma P, Van Kaer L, Das G
PLoS One. 2011 6 (5): e19864

PMID: 21589883 · PMCID: PMC3093409 · 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.

MeSH Terms (11)

Animals Apoptosis Autophagy Cell Proliferation Flow Cytometry Macrophages Mice Mice, Inbred C57BL Mycobacterium tuberculosis T-Lymphocytes Tuberculosis

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