T Cells from Programmed Death-1 Deficient Mice Respond Poorly to Mycobacterium tuberculosis Infection

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Tousif, Sultan ; Singh, Yogesh ; Prasad, Durbaka Vijaya Raghava ; Sharma, Pawan ; Kaer, Luc Van ; Das, Gobardhan
• 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.
  
  
• Subjects:
  Animals Apoptosis Autophagy Cell Proliferation Flow Cytometry Macrophages Mice Mice, Inbred C57BL Mycobacterium Tuberculosis T-Lymphocytes Tuberculosis

  More +
• Source:
  PLoS One. 2011; 6(5).
• Pubmed ID:
  21589883
• Pubmed Central ID:
  PMC3093409
• Document Type:
  Journal Article
• Funding:
  WT01/GD/09/339/GD/OGDP CDC HHS/United States
• Volume:
  6
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:6cb8c5c8deda998cab814c31758ce26aaed96732a649067c745c1fefb2656210
• Download URL:
  https://stacks.cdc.gov/view/cdc/22830/cdc_22830_DS1.pdf
• File Type:
  [PDF - 1.03 MB ]