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
Therapies for tuberculosis and AIDS: myeloid-derived suppressor cells in focus
Anca Dorhoi, … , William Bishai, Nelita du Plessis
Anca Dorhoi, … , William Bishai, Nelita du Plessis
Published May 18, 2020
Citation Information: J Clin Invest. 2020;130(6):2789-2799. https://doi.org/10.1172/JCI136288.
View: Text | PDF
Review Article has an altmetric score of 4

Therapies for tuberculosis and AIDS: myeloid-derived suppressor cells in focus

  • Text
  • PDF
Abstract

The critical role of suppressive myeloid cells in immune regulation has come to the forefront in cancer research, with myeloid-derived suppressor cells (MDSCs) as a main oncology immunotherapeutic target. Recent improvement and standardization of criteria classifying tumor-induced MDSCs have led to unified descriptions and also promoted MDSC research in tuberculosis (TB) and AIDS. Despite convincing evidence on the induction of MDSCs by pathogen-derived molecules and inflammatory mediators in TB and AIDS, very little attention has been given to their therapeutic modulation or roles in vaccination in these diseases. Clinical manifestations in TB are consequences of complex host-pathogen interactions and are substantially affected by HIV infection. Here we summarize the current understanding and knowledge gaps regarding the role of MDSCs in HIV and Mycobacterium tuberculosis (co)infections. We discuss key scientific priorities to enable application of this knowledge to the development of novel strategies to improve vaccine efficacy and/or implementation of enhanced treatment approaches. Building on recent findings and potential for cross-fertilization between oncology and infection biology, we highlight current challenges and untapped opportunities for translating new advances in MDSC research into clinical applications for TB and AIDS.

Authors

Anca Dorhoi, Leigh A. Kotzé, Jay A. Berzofsky, Yongjun Sui, Dmitry I. Gabrilovich, Ankita Garg, Richard Hafner, Shabaana A. Khader, Ulrich E. Schaible, Stefan H.E. Kaufmann, Gerhard Walzl, Manfred B. Lutz, Robert N. Mahon, Suzanne Ostrand-Rosenberg, William Bishai, Nelita du Plessis

×

Figure 1

A schematic view of TB MDSCs and tumor MDSCs within the cellular architecture of the typical granuloma or tumor microenvironment.

Options: View larger image (or click on image) Download as PowerPoint
A schematic view of TB MDSCs and tumor MDSCs within the cellular archite...
The figure compares MDSCs in (A) the solid TME and (B) the TB granuloma microenvironment. M. tuberculosis infects various innate immune cells including macrophages and neutrophils within the granuloma. Macrophages might polarize and differentiate to form foam and multinucleated cells, whose presence is most frequently at the center of mature TB granulomas. Other myeloid cells include DCs that together form the core of the granuloma. Recruited NK cells, B cells, and T cells, including Th1, Th2, and Th17 cells, Tregs, and CD8+ T cells, form the outer cuff, often surrounded by fibroblasts and a collagen matrix (extracellular matrix [ECM]). The type, combination, phenotypes, and arrival timing of immune cells influence pathogen containment and the trajectory of granuloma development. Immune cells produce a range of soluble effector molecules such as cytokines and chemokines. In this inflammatory environment, advanced granulomas develop hypoxia and necrosis, which are followed by tissue destruction. The presence of MDSCs has been reported in necrotic TB granulomas. Similar cellular constituents and crosstalk have been reported for the TME. Apart from malignant cells, the TME contains immune cells, including TAMs and TANs, DCs, NK cells, and T cells, often surrounded by the stroma of fibroblasts and ECM. Both tumor and immune cells produce inflammatory and suppressive signaling molecules such as growth factors, cytokines, chemokines, etc. Tumor-derived immunosuppressive mechanisms are well described, including the presence of MDSCs.

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

Sign up for email alerts

Posted by 6 X users
59 readers on Mendeley
See more details