Characterization of Zymosan-Modulated Neutrophils With Neuroregenerative Properties

Frontiers in Immunology, 2022 · DOI: 10.3389/fimmu.2022.912193 · Published: May 30, 2022

Simple Explanation

This study investigates different types of neutrophils and their potential to help nerve cells regenerate. Neutrophils are immune cells that usually fight infections, but this research found some neutrophils can also protect and repair nerve damage. The researchers used a substance called zymosan to stimulate neutrophils in mice. They found that neutrophils collected at different times after zymosan treatment had distinct characteristics. Some neutrophils showed signs of promoting nerve regeneration. The study used advanced techniques to analyze these neutrophils, including sequencing their RNA and identifying their proteins. This helped the researchers understand how these special neutrophils might work to repair nerve damage.

Study Duration

Not specified

Participants

C57BL/6 WT male mice aged 8-10 weeks

Evidence Level

Not specified

Key Findings

1
3d NF expressed markers of alternative activation and possess neuroprotective/ regenerative properties.
2
3d NF upregulate genes involved in tissue development and wound healing, while 4h NF upregulate genes involved in cytokine production and perpetuation of the immune response.
3
Proteomics analysis revealed that 3d NF and 4h NF also express distinct protein signatures. Adding to our earlier ﬁndings, 3d NF expressed a number of neuroprotective/neuroregenerative candidate proteins that may contribute to their biological functions.

Research Summary

The study characterized two populations of intraperitoneal zymosan-modulated Ly6G+ neutrophils, revealing that 3d NF exhibit features of alternative activation, an immature stage of development, and neuroprotective/neuroregenerative properties, whereas 4h NF express a phenotype consistent with conventional, classically activated neutrophils. Transcriptomic analysis of the 3d NF populations identified transcripts associated with an immature stage of development, alternative activation, and a reparative phenotype, while differential gene ontology pathway analysis confirmed that 3d NF upregulate genes involved in cell survival, immune modulation, and wound healing compared to circulating blood neutrophils or 4h NF. Mass spectrometry proteomic analysis revealed candidate neuroprotective/regenerative factors produced by 3d NF, such as granulins and galectin-1, which had not been previously identified, adding to the growing body of literature attesting to the heterogeneity and functional sub-specialization of neutrophils.

Practical Implications

Therapeutic Potential

Harnessing reparative neutrophils could improve recovery after neurological or tissue injury.

Immunotherapy Development

Understanding neutrophil chemotaxis and signaling could lead to novel immunotherapies.

Targeted Therapies

Modulating neutrophil activation states could provide targeted treatments for various diseases.

Study Limitations

1
The extent to which the alternatively activated neutrophils characterized in these diverse models are biologically or developmentally related to one another, or share common mechanisms of action, remains to be determined.
2
The recruitment of alternatively activated neutrophils to sites of injury and the signaling pathways responsible for their alternatively activated state has yet to be elucidated.
3
The temporal relationship of myeloid cell chemotaxis is also important in the recruitment of reparative or immunosuppressive neutrophils after cardiovascular injury, stroke, certain infections, and cancer

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