Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Tuberculosis lymph node granulomas: using transcriptomics to discover immunopathology paradigms and guide host-directed therapy
James J. Phelan, … , Seónadh O’Leary, Joseph Keane
James J. Phelan, … , Seónadh O’Leary, Joseph Keane
Published August 2, 2021
Citation Information: J Clin Invest. 2021;131(15):e151810. https://doi.org/10.1172/JCI151810.
View: Text | PDF
Commentary

Tuberculosis lymph node granulomas: using transcriptomics to discover immunopathology paradigms and guide host-directed therapy

  • Text
  • PDF
Abstract

Immunometabolism is a burgeoning field of investigation in tuberculosis host defense, susceptibility, and pathophysiology. Unbiased approaches to studying tuberculosis have, as expected, confirmed that pathways of immunometabolism are crucial in these disease processes. In this issue of the JCI, Reichmann et al. studied carefully controlled human lymph node tuberculosis and uncovered Sphingosine kinase 1 as a druggable target of interest that could support the infected host. Future host-directed therapy research might seek to establish the different cellular consequences of sphingolipid pathway manipulation. Animal models will be especially useful to establish the role of this pathway, which might target diseased organs to improve mycobactericidal effect and limit pathology.

Authors

James J. Phelan, Seónadh O’Leary, Joseph Keane

×

Figure 1

Sphingolipid metabolism as a viable HDT option.

Options: View larger image (or click on image) Download as PowerPoint
Sphingolipid metabolism as a viable HDT option.
Identifying additional H...
Identifying additional HDT options, such as DFX and SAHA, through the manipulation of sphingolipid metabolism could be a promising approach in the treatment of TB. Reichmann et al. (5) targeted macrophage/monocyte sphingosine metabolism by inhibiting Sphk1 with PF-543. Sphk1 inhibition controlled Mtb growth, reduced intracellular pH in infected monocytes, and suppressed secretion of CCL2 and MMP-1.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts