LAG-3 potentiates the survival of Mycobacterium tuberculosis in host phagocytes by modulating mitochondrial signaling in an in-vitro granuloma model

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Phillips, Bonnie L.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
    • Other Affiliation: Department of Microbiology and Immunology; Tulane University School of Medicine
  • Gautam, Uma S.
    • Other Affiliation: Tulane National Primate Research Center
  • Bucsan, Allison N.
    • Other Affiliation: Department of Microbiology and Immunology; Tulane University School of Medicine
  • Foreman, Taylor W.
    • Other Affiliation: Department of Microbiology and Immunology; Tulane University School of Medicine
  • Golden, Nadia A.
    • Other Affiliation: Tulane National Primate Research Center
  • Niu, Tianhua
    • Other Affiliation: Department of Biostatistics and Bioinformatics; Tulane University School of Public Health
  • Kaushal, Deepak
    • Other Affiliation: Department of Microbiology and Immunology; Tulane University School of Medicine
  • Mehra, Smriti
    • Other Affiliation: Department of Pathobiological Sciences; Louisiana State University School of Veterinary Medicine
Abstract
  • CD4+ T-cell mediated Th1 immune responses are critical for immunity to TB. The immunomodulatory protein, lymphocyte activation gene-3 (LAG-3) decreases Th1-type immune responses in T-cells. LAG-3 expression is significantly induced in the lungs of macaques with active TB and correlates with increased bacterial burden. Overproduction of LAG-3 can greatly diminish responses and could lead to uncontrolled Mtb replication. To assess the effect of LAG-3 on the progression of Mtb infection, we developed a co-culture system wherein blood-derived macrophages are infected with Mtb and supplemented with macaque blood or lung derived CD4+ T-cells. Silencing LAG-3 signaling in macaque lung CD4+ T-cells enhanced killing of Mtb in co-cultures, accompanied by reduced mitochondrial electron transport and increased IFN-γ expression. Thus, LAG-3 may modulate adaptive immunity to Mtb infection by interfering with the mitochondrial apoptosis pathway. Better understanding this pathway could allow us to circumvent immune features that promote disease.
Date of publication
Keyword
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • PloS One
Journal volume
  • 12
Journal issue
  • 9
Page start
  • e0180413
Language
  • English
ISSN
  • 1932-6203

Relations

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details PubMedCentral-PMC5589099.pdf 2017 Public Download