# The glia-neutrophil axis: an understudied crosstalk in bacteria-induced neuroinflammation

## TL;DR

This review explores how glial cells and neutrophils interact during bacterial CNS infections, highlighting their roles in triggering and potentially controlling neuroinflammation.

## Contribution

The paper emphasizes the underappreciated crosstalk between glia and neutrophils in bacterial neuroinflammation and its potential for therapeutic manipulation.

## Key findings

- Glia produce chemotactic factors that preferentially recruit neutrophils during bacterial CNS infections.
- Neutrophils can further activate glia, creating a feedback loop that exacerbates inflammation.
- Glia and neutrophils may break this cycle by producing anti-inflammatory mediators over time.

## Abstract

Bacterial infections of the central nervous system (CNS) are characterized by rapid and devastating neuroinflammation. While inflammation plays an important physiological role in defense against bacteria, such responses within the confines of the cranium can be lethal. Glial cells, including microglia and astrocytes, can perceive bacteria or their products and then respond in a manner that can promote inflammation, changes to blood–brain barrier integrity, and recruit leukocytes into the CNS. In this review, we have summarized their ability to produce chemotactic factors in response to bacterial components and clinically relevant bacterial pathogens of the CNS. Importantly, we have highlighted the fact that the chemotactic factors produced by bacterially challenged glia tend to preferentially recruit neutrophils, and we have described how such cells could then respond to the presence of bacteria to further promote glial activation and their own recruitment. This then, could form a vicious cycle that precipitates the rapid inflammatory CNS damage associated with bacterial infection. However, it is also becoming apparent that glia, and perhaps neutrophils, can adjust their responses to bacteria temporally in such a way as to break this positive feedback loop, and we have described the available evidence for the delayed production for anti-inflammatory mediators by these cells following challenge. Finally, we have discussed the present limitations in our understanding of these cell–cell interactions and their study that must be overcome before we can manipulate such a glia-neutrophil axis for therapeutic purposes.