Neuron-associated macrophage proliferation in the sensory ganglia is associated with peripheral nerve injury-induced neuropathic pain involving CX3CR1 signaling
- University of Sao Paulo, Brazil
- Washington University in St. Louis, United States
- Université de Montpellier, France
Abstract
Resident macrophages are distributed across all tissues and are highly heterogeneous due to adaptation to different tissue-specific environments. The resident macrophages of the sensory ganglia (sensory neuron-associated macrophages, sNAMs) are in close contact with the cell body of primary sensory neurons and might play physiological and pathophysiological roles. After peripheral nerve injury, there is an increase in the population of macrophage in the sensory ganglia, which have been implicated in different conditions, including neuropathic pain development. However, it is still under debate whether macrophage accumulation in the sensory ganglia after peripheral nerve injury is due to the local proliferation of resident macrophages or a result of blood monocyte infiltration. Here, we confirmed that the number of macrophages increased in the sensory ganglia after the spared nerve injury (SNI) model in mice. Using different approaches, we found that the increase in the number of macrophages in the sensory ganglia after SNI is a consequence of the proliferation of resident CX3CR1+ macrophages, which participate in the development of neuropathic pain, but not due to infiltration of peripheral blood monocytes. These proliferating macrophages are the source of pro-inflammatory cytokines such as TNF and IL-1b. In addition, we found that CX3CR1 signaling is involved in the sNAMs proliferation and neuropathic pain development after peripheral nerve injury. In summary, these results indicated that peripheral nerve injury leads to sNAMs proliferation in the sensory ganglia in a CX3CR1-dependent manner accounting for neuropathic pain development. In conclusion, sNAMs proliferation could be modulated to change pathophysiological conditions such as chronic neuropathic pain.
Data availability
All data generated or analyzed during this study are included in the manuscript. Public scRNA-seq data are available in Gene Expression Omnibus (GEO) database under the series number GSE139103 (Avraham et al. 2020).
-
Satellite glial cells promote regenerative growth in sensory neurons.NCBI Gene Expression Omnibus, GSE139103.
Article and author information
Author details
Thiago Mattar Cunha
Funding
The authors declare that there was no funding for this work.
Ethics
Animal experimentation: Animal care and handling procedures were under the guidelines of the International Association for the Study of Pain for those animals used in pain research and were approved by the Committee for Ethics in Animal Research of the Ribeirao Preto Medical School- University of São Paulo (Process number 002/2017).
Copyright
© 2023, Guimarães et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,003
- views
-
- 481
- downloads
-
- 26
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Neuron-associated macrophage proliferation in the sensory ganglia is associated with peripheral nerve injury-induced neuropathic pain involving CX3CR1 signaling
eLife 12:e78515.
https://doi.org/10.7554/eLife.78515
Further reading
-
- Immunology and Inflammation
Macrophages control intracellular pathogens like Salmonella by using two caspase enzymes at different times during infection.
-
- Immunology and Inflammation
- Medicine
Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, cytometry by time of flight indicated that the frequencies of memory-like Th17 cells (CD45RA−CCR7+IL-17A+CD4+), memory-like CD8+ T cells (CD38+CXCR3−CCR7+Helios−CD127−CD8+) and pro-inflam Macs (CD206−CD163−CD38midCD107alowCD86midHLA-DRmidCD14+) were increased, while the frequencies of anti-inflam Macs (CD206+CD163−CD86midCD33+HLA-DR+CD14+) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b+CD15hiHLA-DRlow) were decreased in the placenta of PE compared with that of normal pregnancy (NP), but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8+ T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80+CD206− pro-inflam Macs with a Folr2+Ccl7+Ccl8+C1qa+C1qb+C1qc+ phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a+Rora+Il1r1+TNF+Cxcr6+S100a4+CD44+ Th17 cells via IGF1–IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8+ T cells but inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+ gMDSCs at the maternal–fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.
