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Updated: Jun 28, 2025
Analysis of Human Natural Killer Cell Metabolism
Published on: June 22, 2020
Differences in nature killer cell response and interference with mitochondrial DNA induced apoptosis in moxifloxacin
Mengqing Wang1, Hao Wu1, Weiwei Jiang1
1Department of Emergency and Critical Care, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Objectives:
As antibiotics become more prevalent, accuracy and safety are critical. Moxifloxacin (MXF) have been reported to have immunomodulatory effects on a variety of immune cells and even anti-proliferative and pro-apoptotic effects, but the mechanism of action is not fully clear.
Methods:
Peripheral blood mononuclear cells (PBMC) from experimental groups of healthy adults (n = 3) were treated with MXF (10ug/ml) in vitro for 24 h. Single-cell sequencing was performed to investigate differences in the response of each immune cell to MXF. Flow cytometry determined differential gene expression in subsets of most damaged NK cells. Pseudo-time analysis identified drivers that influence MXF-stimulated cell differentiation. Detection of mitochondrial DNA and its involvement in the mitochondrial respiratory chain pathway clarifies the origin of MXF-induced stress injury.
Results:
Moxifloxacin-environmental NK cells are markedly reduced: a new subset of NK cells emerges, and immediate-early-response genes in this subset indicate the presence of an early activation response. The inhibitory receptor-dominant subset shows enhanced activation, leading to increased expression of cytokines and chemokines. The near-mature subset showed greater cytotoxicity and the most pronounced cellular damage. CD56bright cells responded by antagonizing the regulation of activation and inhibitory signals, demonstrating a strong cleavage capacity. The severe depletion of mitochondrial genes was focused on apoptosis induced by the mitochondrial respiratory chain complex.
Conclusion:
NK cells exhibit heightened sensitivity to the MXF environment. Different NK subsets upregulate the expression of cytokines and chemokines through different activation pathways. Concurrently, MXF induces impairment of the mitochondrial oxidative phosphorylation system, culminating in apoptosis.
Insights
Moxifloxacin (MXF) significantly impacts natural killer (NK) cells, altering their activation, function, and leading to apoptosis via mitochondrial damage. This study clarifies MXF
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Antibiotic safety and efficacy are paramount, particularly with increasing usage.
- Moxifloxacin (MXF) exhibits known immunomodulatory effects, but its precise mechanisms, especially on immune cells like NK cells, remain unclear.
- Understanding MXF's impact on immune cell function is crucial for predicting and managing potential side effects.
Purpose of the Study:
- To elucidate the specific effects of Moxifloxacin (MXF) on different subsets of human peripheral blood mononuclear cells (PBMCs), with a focus on natural killer (NK) cells.
- To investigate the molecular mechanisms underlying MXF-induced cellular responses, including gene expression, differentiation, and apoptosis.
- To identify the role of mitochondrial pathways in MXF-induced cellular stress and injury.
Main Methods:
- In vitro treatment of human PBMCs with Moxifloxacin (MXF).
- Single-cell RNA sequencing to analyze cellular responses at a granular level.
- Flow cytometry for differential gene expression analysis in NK cell subsets.
- Mitochondrial DNA detection and pathway analysis to assess oxidative stress.
Main Results:
- Moxifloxacin (MXF) treatment led to a marked reduction in specific NK cell populations and the emergence of a novel subset with early activation gene expression.
- Distinct NK cell subsets displayed varied responses, including enhanced activation, increased cytokine/chemokine production, heightened cytotoxicity, and significant cellular damage.
- MXF induced severe depletion of mitochondrial genes, implicating the mitochondrial respiratory chain in apoptosis.
Conclusions:
- Natural killer (NK) cells are highly sensitive to Moxifloxacin (MXF), with different subsets responding via distinct activation pathways.
- MXF disrupts the mitochondrial oxidative phosphorylation system, triggering apoptosis in NK cells.
- The findings highlight the complex immunomodulatory actions of MXF and its potential to induce cellular injury.
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