Immunometabolic Control of Neutrophil Plasticity in Tuberculosis.

Authors

Khaldoun Hamdan, Jasur Rizaev, Dhara N Patel, Swayamsidha Mangaraj, Ahmed Faisal Mutee, Urazbaeva Yulduz, Erdonov Bekmurod, Shefali

Published in

Cell biology international. Volume 50. Issue 9. Pages e70205.

Abstract

The development of tuberculosis (TB) is dictated by a complicated interplay between antimicrobial defense and host-mediated immunopathology. Neutrophils are known to exhibit striking functional plasticity with phenotypes associated with both bacterial containment and tissue damage. However, the mechanisms that connect the granuloma microenvironment to neutrophil fate remain poorly understood. This review aims to fill this gap by integrating emerging evidence that defines immunometabolic adaptation as a key determinant of neutrophil plasticity in TB. The core of this analysis delineates how the spatially organized granuloma characterized by hypoxia, nutrient limitation, iron dysregulation, and extracellular acidosis imposes metabolic pressures that remodel neutrophil function. Environmental signals converge on regulatory networks, including HIF-1α, mTOR/AMPK signaling, glycolytic pathways, the pentose phosphate pathway, and redox control systems, thereby affecting the switch between antimicrobial activity and pathological inflammation. This paradigm presents metabolic rewiring as a potentially important determinant of neutrophil fate in TB and offers a mechanistic view of how protective antimicrobial programs could evolve into dysfunctional states characterized by excessive NETosis, matrix destruction, ferroptotic stress, and tissue injury. Ultimately, a better understanding of these metabolic checkpoints may provide opportunities for the development of host-directed therapeutic approaches to enhance protective neutrophil functions while limiting immunopathology.

PMID:
42677989
Bibliographic data and abstract were imported from PubMed on 01 Sep 2026.

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