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

Area of Science:

• Immunotoxicology
• Environmental Health
• Cellular Metabolism

Background:

• Hexavalent chromium (Cr(VI)) is a significant environmental and occupational hazard impacting immune function.
• The precise cell-intrinsic mechanisms of Cr(VI)-induced macrophage alterations, including immunometabolic and mitochondrial changes, are not fully understood.

Purpose of the Study:

• To investigate the effects of Cr(VI) exposure on macrophage morphology, polarization, energy metabolism, and mitochondrial integrity in vitro.
• To elucidate the cell-intrinsic mechanisms underlying Cr(VI)-induced immunotoxicity.

Main Methods:

• In vitro exposure of macrophages to Cr(VI).
• Assessment of macrophage morphology and M1/M2 polarization markers (TNF-α, CD36, CD80, VEGFb).
• Analysis of cellular energy metabolism (ATP production, glucose uptake) and mitochondrial function (membrane potential, oxidative stress).

Main Results:

• Cr(VI) exposure induced morphological changes and a shift towards M1 macrophage polarization.
• Key M1 biomarkers increased while M2 biomarkers decreased post-Cr(VI) exposure.
• Impaired energy metabolism, reduced ATP production, increased glycolysis despite higher glucose uptake, and mitochondrial damage were observed.

Conclusions:

• Cr(VI) exposure dysregulates macrophage polarization and immunometabolism, leading to impaired energy production.
• Mitochondrial dysfunction and oxidative stress are key components of Cr(VI)-induced macrophage toxicity.
• Findings underscore the environmental risks of Cr(VI) and the need for mitigation strategies.