title: CXCR3-dependent plasma blast migration to the central nervous system during viral encephalomyelitis.
abstract: Immunoglobulin in cerebral spinal fluid and antibody secreting cells (ASC) within the central nervous system (CNS) parenchyma are common hallmarks of microbial infections and autoimmune disorders. However, the signals directing ASC migration into the inflamed CNS are poorly characterized. This study demonstrates that CXCR3 mediates CNS accumulation of ASC during neurotropic coronavirus-induced encephalomyelitis. Expansion of CXCR3-expressing ASC in draining lymph nodes prior to accumulation within the CNS was consistent with their recruitment by sustained expression of CXCR3 ligands during viral persistence. Both total and virus-specific ASC were reduced greater than 80% in the CNS of infected CXCR3(-/-) mice. Similar T cell CNS recruitment and local T cell-dependent antiviral activity further indicated that the ASC migration defect was T cell independent. Furthermore, in contrast to the reduction of ASC in the CNS, neither virus-specific ASC trafficking to bone marrow nor antiviral serum antibody was reduced relative to levels in control mice. Impaired ASC recruitment into the CNS of infected CXCR3(-/-) mice coincided with elevated levels of persisting viral RNA, sustained infectious virus, increased clinical disease, and mortality. These results demonstrate that CXCR3 ligands are indispensable for recruitment of activated ASC into the inflamed CNS and highlight their local protective role during persistent infection.
authors.affiliation: Department of Neuroscience, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, NC30, Cleveland, OH 44195, USA.
authors.forename: Cristina P
authors.initials: CP
authors.lastname: Marques
authors.forename: Parul
authors.initials: P
authors.lastname: Kapil
authors.forename: David R
authors.initials: DR
authors.lastname: Hinton
authors.forename: Claudia
authors.initials: C
authors.lastname: Hindinger
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Phares
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stohlman
authors.forename: Cornelia C
authors.initials: CC
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology*; D018352:Coronavirus Infections / Q000276:immunology / Q000821:virology; D004679:Encephalomyelitis / Q000276:immunology* / Q000821:virology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D006517:Murine hepatitis virus / Q000276:immunology* / Q000472:pathogenicity; D010950:Plasma Cells / Q000166:cytology / Q000502:physiology*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D054367:Receptors, CXCR3