title: Protective role of CX3CR1 signalling in resident cells of the central nervous system during experimental herpes simplex virus encephalitis.
abstract: CX3CR1 is an important chemokine receptor expressed on the surface of microglia and blood leukocytes, including monocytes. Signalling through this receptor influences the immune activity of microglia and monocyte trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CX3CR1 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CX3CR1 expressed in resident cells of the CNS or peripheral monocytes in protection against HSE remains unclear. To dissect the role of CX3CR1 during HSE, we reconstituted irradiated C57BL/6 WT and CX3CR1-/- mice with CX3CR1-/- (CX3CR1-/-→WT) and WT (WT→CX3CR1-/-) bone marrow cells, respectively. Our results showed that following intranasal infection with 1.2×106 p.f.u. of HSV-1, mortality rates were significantly higher in CX3CR1-/- (61.7 %) and WT→CX3CR1-/- (66.2 %) compared to WT (16.6 %; P=0.012 and P=0.016, respectively) and CX3CR1-/-→WT animals (20 %; P=0.013 and P=0.011, respectively). Higher mortality rates in CX3CR1-/- and WT→CX3CR1-/- mice were associated with increased infectious viral titres and wider HSV dissemination in brains, as well as an overproduction of inflammatory cytokines and chemokines including IL-1β, IL-6, IFN-γ, C-C motif ligand 2 and C-C motif ligand 5. Furthermore, CX3CR1 deficiency in resident cells of the CNS resulted in excessive and sustained Ly6Chi inflammatory monocyte and neutrophil infiltration into the brain. These data suggest that CX3CR1 deficiency in resident cells of the CNS affects mouse survival, HSV-1 replication control and cerebral inflammatory response whereas its deficiency in the haematopoietic system does not appear to influence the outcome of HSE.
authors.affiliation: Research Center in Infectious Diseases of the CHU of Quebec and Laval University, 2705 Boul Laurier, Quebec City, QC G1V 4G2, Canada.
authors.forename: Rafik
authors.initials: R
authors.lastname: Menasria
authors.affiliation: Research Center in Infectious Diseases of the CHU of Quebec and Laval University, 2705 Boul Laurier, Quebec City, QC G1V 4G2, Canada.
authors.forename: Coraline
authors.initials: C
authors.lastname: Canivet
authors.affiliation: Research Center in Infectious Diseases of the CHU of Quebec and Laval University, 2705 Boul Laurier, Quebec City, QC G1V 4G2, Canada.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Piret
authors.affiliation: Laboratory of Innate Immunology of the CHU of Quebec and Laval University, 2705 Boul Laurier, Quebec City, QC G1V 4G2, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Gosselin
authors.affiliation: Research Center in Infectious Diseases of the CHU of Quebec and Laval University, 2705 Boul Laurier, Quebec City, QC G1V 4G2, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000821:virology; D001921:Brain / Q000276:immunology* / Q000821:virology; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020803:Encephalitis, Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017628:Microglia / Q000276:immunology / Q000821:virology; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D000073883:CX3C Chemokine Receptor 1; D018925:Chemokines; C471885:Cx3cr1 protein, mouse; D016207:Cytokines; D019707:Receptors, Chemokine