Lymphocytic choriomeningitis virus (LCMV) infection of CNS glial cells results in TLR2-MyD88/Mal-dependent inflammatory responses
Immunology & Virology Program
Department of Medicine, Division of Infectious Diseases and Immunology; Department of Pediatrics; Department of Cancer Biology
Medical Subject Headings
Animals; Astrocytes; Chemokines; Histocompatibility Antigens Class II; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; Myelin Proteins; Myeloid Differentiation Factor 88; Proteolipids; Specific Pathogen-Free Organisms; Toll-Like Receptor 2; Toll-Like Receptor 3; Toll-Like Receptor 4; Up-Regulation
Cancer Biology | Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
In response to invading pathogens, Toll-like receptors (TLR) play a critical role in the initiation of the innate immune response, which can be either beneficial or detrimental to the host. In the present study, we demonstrated that central nervous system (CNS) glial cells are activated by Lymphocytic Choriomeningitis Virus (LCMV) in a TLR2-MyD88/Mal-dependent manner. Specifically, in response to LCMV, both astrocytes and microglial cells isolated from wild-type (WT) mice produced chemokines, such as MCP-1, RANTES and TNF-alpha. Similar responses occurred in TLR3 KO and TLR4 KO glial cells. In striking contrast, both astrocytes and microglial cells isolated from mice deficient in TLR2, MyD88, and Mal did not produce any of these chemokines. In addition, LCMV infection of glial cells induced up-regulation of TLR2, MHC class-I and II, CD40, CD86 in a MyD88-dependent manner. These results define a functional role for TLR signaling in viral infection-induced activation of CNS glial cells as well as for the immunopathology in the CNS.
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Citation: J Neuroimmunol. 2008 Feb;194(1-2):70-82. Link to article on publisher's site
Zhou, Shenghua; Halle, Annett; Kurt-Jones, Evelyn A.; Cerny, Anna M.; Porpiglia, Ermelinda; Rogers, Michael; Golenbock, Douglas; and Finberg, Robert W., "Lymphocytic choriomeningitis virus (LCMV) infection of CNS glial cells results in TLR2-MyD88/Mal-dependent inflammatory responses" (2008). GSBS Student Publications. Paper 1388.