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Annual Review of Immunology

Volume 43, 2025

Macrophage Differentiation and Metabolic Adaptation in Mycobacterial Infections

  • Anne Kathrin Lösslein1,2 and Philipp Henneke1,2,3
  • 1Institute for Infection Prevention and Control, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; email: [email protected] 2Center for Chronic Immunodeficiency, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany 3Institute for Immunodeficiency, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • Vol. 43:423-450 (Volume publication date April 2025)
  • First published as a Review in Advance on February 27, 2025
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

The adaptation of macrophages—the most common tissue-resident immune cells—to metabolic and microbial cues with high local variability is essential for the maintenance of organ integrity. In homeostasis, macrophages show largely predictable tissue-specific differentiation, as recently revealed by multidimensional methods. However, chronic infections with human-adapted pathogens substantially contribute to the differentiation complexity of tissue macrophages, which has been only partially resolved. Specifically, the response to mycobacterial species—which range from (with highest specificity for humans, broad organ tropism, yet tissue-specific disease phenotypes) to environmental mycobacteria with humans as accidental hosts—may serve as a paradigm of tissue macrophage adaptation mechanisms. While mycobacterial species-specific tissue preferences are partially related to the mode of acquisition and pathogen characteristics, evolutionary convergence with macrophages driven by metabolic features of the target organ likely contributes to infection resistance and immunopathology. In this review, we unravel the mechanisms of tissue-specific macrophage differentiation and its limitations in mycobacterial infections.

Keyword(s): granuloma, macrophages, monocyte development, mycobacteria, tissue immunity, tissue niche
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2025-04-25
2025-06-20
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/content/journals/10.1146/annurev-immunol-082323-120757
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Macrophage Differentiation and Metabolic Adaptation in Mycobacterial Infections
Annual Review of Immunology 43, 423 (2025); https://doi.org/10.1146/annurev-immunol-082323-120757
/content/journals/10.1146/annurev-immunol-082323-120757
/content/journals/10.1146/annurev-immunol-082323-120757
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