Chromium(VI) Modulates Macrophage Polarization and Metabolic Reprogramming to Impair Immune Function

TL;DR

Chromium(VI) exposure alters macrophage function and metabolism, leading to immune dysfunction and environmental health risks.

Contribution

This study reveals how Cr(VI) induces M1 polarization and metabolic reprogramming in macrophages, impairing immune function.

Findings

Cr(VI) exposure increases M1 markers like TNF-α, CD36, and CD80 while decreasing M2 marker VEGFb.

Cr(VI) impairs ATP production and shifts macrophage metabolism toward glycolysis despite increased glucose uptake.

Mitochondrial damage and oxidative stress are observed, contributing to Cr(VI)-induced immunotoxicity.

Abstract

Hexavalent chromium (Cr(VI)) is a recognized environmental and occupational hazard with significant implications for immune function. However, the cell-intrinsic mechanisms by which Cr(VI) coordinately reshapes macrophage polarization together with immunometabolic and mitochondrial alterations remain incompletely characterized. This study investigated how Cr(VI) exposure influences macrophage morphology, polarization, energy metabolism, and mitochondrial integrity using an in vitro model. Macrophages exposed to Cr(VI) exhibited morphological changes, including pseudopod growth and fusiform shapes, alongside a shift toward M1-type polarization. Key M1 associated biomarkers, including TNF-α, CD36, and CD80, increased 24 h after Cr(VI) exposure, whereas the M2 associated VEGFb decreased. Cr(VI) exposure also impaired energy metabolism, reducing ATP production and shifting metabolism towards glycolysis, despite increased glucose uptake. Mitochondrial damage, membrane potential collapse, and elevated oxidative stress further highlighted the immunotoxic effects of Cr(VI). Cr(VI) exposure may drive a metabolic shift in macrophages toward less efficient energy production pathways, such as glycolysis. These findings provide critical insights into Cr(VI)-induced macrophage dysfunction and emphasize the environmental risks associated with Cr(VI) pollution, underscoring the need for further mechanistic research and mitigation strategies to safeguard public health.

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