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T Cells from Programmed Death-1 Deficient Mice Respond Poorly to Mycobacterium tuberculosis Infection
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May 12 2011
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Source: PLoS One. 2011; 6(5).
[PDF-1.03 MB]
Details:
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Alternative Title:PLoS One
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Personal Author:
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Description: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.
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Pubmed ID:21589883
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Pubmed Central ID:PMC3093409
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Volume:6
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Issue:5
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