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Updated: Oct 2, 2025
Real-Time Measurement of the Mitochondrial Bioenergetic Profile of Neutrophils
Published on: June 2, 2023
Increased Dietary Manganese Impairs Neutrophil Extracellular Trap Formation Rendering Neutrophils Ineffective at
Andrew J Monteith1, Jeanette M Miller1, William N Beavers1,2
1Department of Pathology, Microbiology, & Immunology, Vanderbilt University Medical Centergrid.412807.8, Nashville, Tennessee, USA.
Abstract:
Dietary metals can modify the risk to infection. Previously, we demonstrated that heightened dietary manganese (Mn) during systemic Staphylococcus aureus infection increases S. aureus virulence. However, immune cells also operate in these same environments and the effect of dietary Mn on neutrophil function in vivo has not been assessed. This study reveals that increased concentrations of Mn impairs mitochondrial respiration and superoxide production in neutrophils responding to S. aureus. As a result, high Mn accelerates primary degranulation, while impairing suicidal neutrophil extracellular trap (NET) formation, which decreases bactericidal activity. In vivo, elevated dietary Mn accumulated extracellularly in the heart, indicating that excess Mn may be more bioavailable in the heart. Coinciding with this phenotype, neutrophil function in the heart was most impacted by a high Mn diet, as neutrophils produced lower levels of mitochondrial superoxide and underwent less suicidal NET formation. Consistent with an ineffective neutrophil response when mice are on a high Mn diet, S. aureus burdens were increased in the heart and mice were more susceptible to systemic infection. Therefore, elevated dietary Mn not only affects S. aureus but also renders neutrophils less capable of restricting staphylococcal infection.
Insights
High dietary manganese (Mn) impairs neutrophil function, reducing the body's ability to fight Staphylococcus aureus infections. This excess manganese hinders bacterial clearance, increasing infection susceptibility.
Area of Science:
- Immunology
- Nutritional Science
- Microbiology
Background:
- Dietary metals influence infection risk.
- Elevated dietary manganese (Mn) previously shown to increase Staphylococcus aureus virulence.
- The impact of dietary Mn on neutrophil function during infection was unassessed.
Purpose of the Study:
- To investigate the effect of dietary manganese on neutrophil function during Staphylococcus aureus infection.
- To determine if high dietary manganese impacts neutrophil mitochondrial respiration and superoxide production.
- To assess the consequences of impaired neutrophil function on bacterial clearance and infection severity.
Main Methods:
- Mice were fed diets with varying manganese concentrations.
- Neutrophil function, including mitochondrial respiration, superoxide production, degranulation, and neutrophil extracellular trap (NET) formation, was assessed.
- Bacterial burdens and host susceptibility to systemic S. aureus infection were quantified.
- Manganese accumulation in host tissues was analyzed.
Main Results:
- High dietary manganese impaired neutrophil mitochondrial respiration and superoxide production.
- Excess manganese accelerated neutrophil degranulation but inhibited NET formation, reducing bactericidal activity.
- Elevated manganese accumulated in the heart, disproportionately affecting cardiac neutrophil function.
- Mice on high manganese diets exhibited increased S. aureus burdens in the heart and heightened susceptibility to systemic infection.
Conclusions:
- Elevated dietary manganese compromises neutrophil antimicrobial functions, including NET formation and superoxide production.
- High manganese diets render neutrophils less effective in controlling Staphylococcus aureus infections.
- Excess manganese bioavailability, particularly in the heart, exacerbates infection outcomes.
