# Polystyrene Nanoplastics Increase Macrophage Bactericidal Activity Through a Mechanism Involving Reactive Oxygen Species and Itaconate

## TL;DR

Polystyrene nanoplastics boost macrophage ability to kill bacteria by increasing reactive oxygen species and itaconate production.

## Contribution

The study reveals a novel mechanism by which nanoplastics enhance macrophage bactericidal activity through ROS and itaconate.

## Key findings

- Polystyrene nanoplastics are internalized into macrophage organelles like endosomes and lysosomes.
- Nanoplastics increase macrophage bactericidal activity via reactive oxygen species production.
- Itaconate, produced via aconitate decarboxylase 1, plays a key role in enhanced bacterial killing.

## Abstract

Nanoplastics are persistent environmental pollutants with potential risks to human health. Due to their small size, nanoplastics are internalized by macrophages, potentially altering their function. In this study we found that, in macrophages, 50 nm polystyrene nanoplastics were predominantly present in endosomes, lysosomes, and in the endoplasmic reticulum. Internalization of polystyrene nanoplastics increased the bactericidal activity of macrophages, which was inhibited by the NADPH oxidase inhibitor diphenyleneiodonium. Consistently, measurements of cellular and mitochondrial reactive oxygen species by flow cytometry revealed that polystyrene nanoplastics induced reactive oxygen species production in macrophages. In contrast, internalization of polystyrene nanoplastics reduced the levels of nitric oxide released by macrophages in response to E. coli. Internalization of polystyrene nanoplastics followed by the addition of E. coli induced high expression levels of the aconitate decarboxylase 1 gene. In the absence of this gene, killing of E. coli by macrophages exposed to polystyrene nanoplastics was significantly attenuated with respect to control macrophages, indicating a role for the mitochondrial metabolite itaconate in the increased bactericidal activity of macrophages exposed to polystyrene nanoplastics. Collectively, our results indicate that exposure of macrophages to polystyrene nanoplastics increases their bactericidal activity through the production of reactive oxygen species and of itaconate.