Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation
- PMID: 19228962
- PMCID: PMC6666330
- DOI: 10.1523/JNEUROSCI.3567-08.2009
Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation
Abstract
In inflammatory diseases occurring outside the CNS, communication between the periphery and the brain via humoral and/or neural routes results in central neural changes and associated behavioral alterations. We have recently identified another immune-to-CNS communication pathway in the setting of organ-centered peripheral inflammation: namely, the entrance of immune cells into the brain. In our current study, using a mouse model of inflammatory liver injury, we have confirmed the significant infiltration of activated monocytes into the brain in mice with hepatic inflammation and have defined the mechanism that mediates this trafficking of monocytes. Specifically, we show that in the presence of hepatic inflammation, mice demonstrate elevated cerebral monocyte chemoattractant protein (MCP)-1 levels, as well as increased numbers of circulating CCR2-expressing monocytes. Cerebral recruitment of monocytes was abolished in inflamed mice that lacked MCP-1/CCL2 or CCR2. Furthermore, in mice with hepatic inflammation, microglia were activated and produced MCP-1/CCL2 before cerebral monocyte infiltration. Moreover, peripheral tumor necrosis factor (TNF)alpha signaling was required to stimulate microglia to produce MCP-1/CCL2. TNFalpha signaling via TNF receptor 1 (TNFR1) is required for these observed effects since in TNFR1 deficient mice with hepatic inflammation, microglial expression of MCP-1/CCL2 and cerebral monocyte recruitment were both markedly inhibited, whereas there was no inhibition in TNFR2 deficient mice. Our results identify the existence of a novel immune-to-CNS communication pathway occurring in the setting of peripheral organ-centered inflammation which may have specific implications for the development of alterations in cerebral neurotransmission commonly encountered in numerous inflammatory diseases occurring outside the CNS.
Figures
![Figure 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430001.gif)
![Figure 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430002.gif)
![Figure 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430003.gif)
![Figure 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430004.gif)
![Figure 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430005.gif)
![Figure 6.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430006.gif)
![Figure 7.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430007.gif)
![Figure 8.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430008.gif)
![Figure 9.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430009.gif)
![Figure 10.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430010.gif)
![Figure 11.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430011.gif)
![Figure 12.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6666330/bin/zns0070960430012.gif)
Similar articles
-
Role of MCP-1 and CCR2 in alcohol neurotoxicity.Pharmacol Res. 2019 Jan;139:360-366. doi: 10.1016/j.phrs.2018.11.030. Epub 2018 Nov 22. Pharmacol Res. 2019. PMID: 30472461 Free PMC article. Review.
-
Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis.Arterioscler Thromb Vasc Biol. 2017 Jul;37(7):1315-1322. doi: 10.1161/ATVBAHA.116.308925. Epub 2017 Apr 27. Arterioscler Thromb Vasc Biol. 2017. PMID: 28450294
-
Liver-brain interactions in inflammatory liver diseases: implications for fatigue and mood disorders.Brain Behav Immun. 2014 Jan;35:9-20. doi: 10.1016/j.bbi.2013.10.009. Epub 2013 Oct 16. Brain Behav Immun. 2014. PMID: 24140301 Review.
-
Aortic adventitial fibroblasts participate in angiotensin-induced vascular wall inflammation and remodeling.J Vasc Res. 2011;48(3):261-72. doi: 10.1159/000320358. Epub 2010 Nov 23. J Vasc Res. 2011. PMID: 21099231 Free PMC article.
-
Regulation of inflammatory monocyte/macrophage recruitment from the bone marrow during murine cytomegalovirus infection: role for type I interferons in localized induction of CCR2 ligands.J Immunol. 2009 Aug 15;183(4):2810-7. doi: 10.4049/jimmunol.0900205. Epub 2009 Jul 20. J Immunol. 2009. PMID: 19620305 Free PMC article.
Cited by
-
A longer time to relapse is associated with a larger increase in differences between paired primary and recurrent IDH wild-type glioblastomas at both the transcriptomic and genomic levels.Acta Neuropathol Commun. 2024 May 18;12(1):77. doi: 10.1186/s40478-024-01790-3. Acta Neuropathol Commun. 2024. PMID: 38762464 Free PMC article.
-
Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis.Res Sq [Preprint]. 2024 Mar 12:rs.3.rs-3952442. doi: 10.21203/rs.3.rs-3952442/v1. Res Sq. 2024. PMID: 38559083 Free PMC article. Preprint.
-
Immunological Analysis of Postoperative Delirium after Thoracic Aortic Surgery.J Chest Surg. 2024 May 5;57(3):263-271. doi: 10.5090/jcs.23.159. Epub 2024 Mar 13. J Chest Surg. 2024. PMID: 38472124 Free PMC article.
-
Deficiency in astrocyte CCL2 production reduces neuroimmune control of Toxoplasma gondii infection.PLoS Pathog. 2024 Jan 11;20(1):e1011710. doi: 10.1371/journal.ppat.1011710. eCollection 2024 Jan. PLoS Pathog. 2024. PMID: 38206985 Free PMC article.
-
Gut liver brain axis in diseases: the implications for therapeutic interventions.Signal Transduct Target Ther. 2023 Dec 6;8(1):443. doi: 10.1038/s41392-023-01673-4. Signal Transduct Target Ther. 2023. PMID: 38057297 Free PMC article. Review.
References
-
- Abe T, Arai T, Ogawa A, Hiromatsu T, Masuda A, Matsuguchi T, Nimura Y, Yoshikai Y. Kupffer cell derived interleukin 10 is responsible for impaired bacterial clearance in bile duct ligated mice. Hepatology. 2004;40:414–423. - PubMed
-
- Aggarwal BB. Signaling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol. 2003;3:745–756. - PubMed
-
- Ahmed Z, Shaw G, Sharma VP, Yang C, McGowan E, Dickson DW. Actin-binding proteins Coronin-1a and IBA-1 are effective microglial markers for immunohistochemistry. J Histochem Cytochem. 2007;55:687–700. - PubMed
-
- Banisadr G, Quéraud-Lesaux F, Boutterin MC, Pélaprat D, Zalc B, Rostène W, Haour F, Parsadaniantz SM. Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain. J Neurochem. 2002;81:257–269. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous