Lymphocytic choriomeningitis virus (LCMV) infection of CNS glial cells results in TLR2-MyD88/Mal-dependent inflammatory responses.
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.
Zhou
Shenghua
S
Department of Medicine, University of Massachusetts Medical Center, 364 Plantation Street, Lazare Research Building, Worcester, MA 01605, USA. shenghua.zhou@umassmed.edu
Halle
Annett
A
Kurt-Jones
Evelyn A
EA
Cerny
Anna M
AM
Porpiglia
Ermelinda
E
Rogers
Michael
M
Golenbock
Douglas T
DT
Finberg
Robert W
RW
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000503:physiopathology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009185:Myelin Proteins / Q000172:deficiency / Q000502:physiology*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000502:physiology*; D011510:Proteolipids / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000172:deficiency / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000502:physiology; D015854:Up-Regulation
D018925:Chemokines; D000949:Histocompatibility Antigens Class II; C569027:Mal protein, mouse; D026901:Membrane Transport Proteins; C507780:Myd88 protein, mouse; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D053594:Myeloid Differentiation Factor 88; D011510:Proteolipids; C519703:TLR3 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4