Viruses selectively upregulate Toll-like receptors in the central nervous system.
The resting CNS is an immunospecialized environment, devoid of most immune processes, although substantial inflammatory responses can be initiated. The innate immune mechanisms mediating recognition of CNS infections are unknown. This study provides a comprehensive analysis of Toll-like receptor (TLR) gene expression in the resting and virus-infected murine CNS. TLR transcripts were expressed in the resting CNS with strikingly high expression of TLR 3. Extraneural infection with neuroinvasive Semliki Forest virus resulted in CNS infection followed by rapid selective upregulation of TLR gene expression. Upregulation was independent of T-cell responses. Upregulation of TLR gene expression was also observed following rabies virus infection. TLR upregulation was appropriate to the pathogen and proportional to the virus load. Upregulation of TLR 3 and 9 was dependent upon the type-I interferon response and may act to increase the threshold of sensitivity to detect virus infection in cells surrounding virally infected cells.
McKimmie
Clive S
CS
Centre for Infectious Diseases, College of Medicine and Veterinary Medicine, University of Edinburgh, UK.
Johnson
Nicholas
N
Fooks
Anthony R
AR
Fazakerley
John K
JK
D018354:Alphavirus Infections / Q000276:immunology; D000818:Animals; D001921:Brain / Q000276:immunology*; D020805:Central Nervous System Viral Diseases / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D007370:Interferon Type I / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D011818:Rabies / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012672:Semliki forest virus; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495370:Tlr9 protein, mouse; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors