Lymphocytic choriomeningitis and alpha-chemokines
1Department of Clinical and Experimental Medicine, University of Pisa, Italy.
Insights
Interferon gamma-induced protein 10 (IP-10) and its receptor CXCR3 are key in lymphocytic choriomeningitis (LCM). Astrocytes are central to the CNS immune response during LCM, interacting with T cells.
Area of Science:
- Neuroimmunology
- Virology
- Immunology
Background:
- Lymphocytic choriomeningitis (LCM) involves immune and central nervous system (CNS) cells.
- Interferon gamma-induced protein 10 (IP-10) and its receptor CXCR3 are implicated in LCM pathogenesis.
- The roles of CNS resident cells in LCM inflammation are not fully understood.
Purpose of the Study:
- To investigate the role of IP-10/CXCR3 axis in LCM.
- To identify the cellular sources of IP-10 within the CNS during LCM.
- To elucidate the interplay between CNS resident cells and infiltrating immune cells.
Main Methods:
- Murine model of LCM.
- Immunohistochemistry and flow cytometry to analyze immune cell infiltration and CNS cell activation.
- Gene expression analysis to quantify IP-10 production.
Main Results:
- IP-10 is crucial for effector T cell accumulation at CNS inflammation sites during LCM.
- Astrocytes are the primary producers of IP-10 in the neural parenchyma.
- Microglial cells and bone marrow-derived cells are not significant IP-10 producers in this context.
- A bidirectional interplay exists between CNS resident astrocytes and virus-specific T cells.
Conclusions:
- The IP-10/CXCR3 pathway is critical for T cell recruitment to the CNS during LCM.
- Astrocytes play an active role in the local antiviral immune response within the CNS.
- This study highlights astrocytes as key mediators in neuroinflammation during viral infections.
Abstract:
IP-10 and its receptor CXCR3 play an important role in lymphocytic choriomeningitis (LCM). During the course of LCM in mice not only cells of the immune system but also central nervous system (CNS) resident cells are actively involved in both the pro- and the counter-inflammatory immune circuits. A central role for IP-10 in regulating the accumulation of effector T cells at sites of CNS inflammation, with no apparent compensatory effect of other CXCR3 ligands, has been shown. The producers of IP-10 are mainly resident cells of the CNS, and astrocytes are the dominant expressors in the neural parenchyma, not microglial cells or recruited bone marrow-derived cell types. These results are consistent with a mode suggesting a bidirectional interplay between resident cells of the CNS and the recruited virus-specific T cells with astrocytes as active participants in the local antiviral host response.
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