title: Knockout of fractalkine receptor Cx3cr1 does not alter disease or microglial activation in prion-infected mice.
abstract: Microglial activation is a hallmark of the neuroimmunological response to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and prion disease. The CX3C chemokine axis consists of fractalkine (CX3CL1) and its receptor (CX3CR1); these are expressed by neurons and microglia respectively, and are known to modulate microglial activation. In prion-infected mice, both Cx3cr1 and Cx3cl1 are altered, suggesting a role in disease. To investigate the influence of CX3C axis signalling on prion disease, we infected Cx3cr1 knockout (Cx3cr1-KO) and control mice with scrapie strains 22L and RML. Deletion of Cx3cr1 had no effect on development of clinical signs or disease incubation period. In addition, comparison of brain tissue from Cx3cr1-KO and control mice revealed no significant differences in cytokine levels, spongiosis, deposition of disease-associated prion protein or microglial activation. Thus, microglial activation during prion infection did not require CX3C axis signalling.
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Striebel
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: Race
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Carroll
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Phillips
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Chesebro
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology*; D017096:Prion Diseases / Q000235:genetics* / Q000473:pathology*; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D018121:Receptors, Cytokine / Q000172:deficiency / Q000378:metabolism; D015728:Receptors, HIV / Q000172:deficiency / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015728:Receptors, HIV