Format

Send to

Choose Destination
J Neurosci. 2009 Feb 18;29(7):2089-102. 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.

Author information

1
Immunology Research Group, Department of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1.

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.

PMID:
19228962
DOI:
10.1523/JNEUROSCI.3567-08.2009
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center