PUBLICATION
Peripheral NOD-like receptor deficient inflammatory macrophages trigger neutrophil infiltration into the brain disrupting daytime locomotion
- Authors
- Kwon, V., Cai, P., Dixon, C.T., Hamlin, V., Spencer, C.G., Rojas, A.M., Hamilton, M., Shiau, C.E.
- ID
- ZDB-PUB-220518-2
- Date
- 2022
- Source
- Communications biology 5: 464 (Journal)
- Registered Authors
- Shiau, Celia
- Keywords
- none
- Datasets
- GEO:GSE179883
- MeSH Terms
-
- NLR Proteins*
- Animals
- Inflammation/genetics
- Macrophages
- Brain
- Locomotion
- Neutrophil Infiltration
- Zebrafish*
- PubMed
- 35577844 Full text @ Commun Biol
Citation
Kwon, V., Cai, P., Dixon, C.T., Hamlin, V., Spencer, C.G., Rojas, A.M., Hamilton, M., Shiau, C.E. (2022) Peripheral NOD-like receptor deficient inflammatory macrophages trigger neutrophil infiltration into the brain disrupting daytime locomotion. Communications biology. 5:464.
Abstract
Inflammation is known to disrupt normal behavior, yet the underlying neuroimmune interactions remain elusive. Here, we investigated whether inappropriate macrophage-evoked inflammation alters CNS control of daily-life animal locomotion using a set of zebrafish mutants selected for specific macrophage dysfunction and microglia deficiency. Large-scale genetic and computational analyses revealed that NOD-like receptor nlrc3l mutants are capable of normal motility and visuomotor response, but preferentially swim less in the daytime, suggesting possible low motivation rather than physical impairment. Examining their brain activities and structures implicates impaired dopaminergic descending circuits, where neutrophils abnormally infiltrate. Furthermore, neutrophil depletion recovered daytime locomotion. Restoring wild-type macrophages reversed behavioral and neutrophil aberrations, while three other microglia-lacking mutants failed to phenocopy nlrc3l mutants. Overall, we reveal how peripheral inflammatory macrophages with elevated pro-inflammatory cues (including il1β, tnfα, cxcl8a) in the absence of microglia co-opt neutrophils to infiltrate the brain, thereby potentially enabling local circuitry modulation affecting daytime locomotion.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping