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
  • Locomotion
  • Animals
  • Macrophages
  • Inflammation/genetics
  • Zebrafish*
  • Brain
  • NLR Proteins*
  • Neutrophil Infiltration
(all 8)
PubMed
35577844 Full text @ Commun Biol
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
Figures
Figure Gallery (8 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
csf3rMO4-csf3rMRPHLNO
spi1bMO1-spi1bMRPHLNO
1 - 2 of 2
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Fish
No data available
Antibodies
Orthology
No data available
Engineered Foreign Genes
Marker Marker Type Name
DsRedEFGDsRed
EGFPEFGEGFP
GCaMPEFGGCaMP
1 - 3 of 3
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Mapping
No data available
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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.