# Accumulation of free nuclei denotes defective phagocytic capacity of macrophages and occurs after infection with Listeria monocytogenes and lymphocytic choriomeningitis virus

## TL;DR

This paper shows that free nuclei in blood can signal poor macrophage function, which is linked to severe infections like Listeria.

## Contribution

The study introduces free nuclei in blood as a novel, noninvasive biomarker for defective macrophage phagocytosis.

## Key findings

- Free nuclei in blood correlate with reduced macrophage function and poor infection outcomes.
- Macrophage-depleted and interferon-gamma-deficient mice show increased free nuclei and severe disease.
- Free nuclei originate from bone marrow-derived cells and indicate host vulnerability to infection.

## Abstract

Efficient phagocytosis of pathogens is a key effector function of the innate immune system. Impaired phagocytic activity can result in uncontrolled pathogen proliferation and life-threatening infections. However, reliable methods to detect early dysfunction of the phagocytic system in vivo are limited. Here, we used a mouse model of Listeria monocytogenes infection to determine blood parameters which correlate with limited macrophage function. We found that lack of macrophages led to accumulation of nuclei in the blood. Further analysis of nuclei revealed that these nuclei were released from bone marrow-derived cells. Macrophage-depleted mice and interferon-gamma-deficient mice, which are known to have reduced phagocytotic capacity, showed increased amounts of free nuclei. This was associated with lethal outcome and occurrence of acute hepatopathy in these mice after Listeria monocytogenes infection. Our findings highlight a simple and noninvasive method to assess macrophage phagocytic function in vivo, which should be assessed in further murine and human studies as a tool for predicting host vulnerability to infection.