CXCR3-Dependent Plasma Blast Migration to the Central Nervous System during Viral Encephalomyelitis

Marques, CP; Kapil, P; Hinton, DR; Hindinger, C; Nutt, SL; Ransohoff, RM; Phares, TW; Stohlman, SA; Bergmann, CC

Author(s): Marques, CP; Kapil, P; Hinton, DR; Hindinger, C; Nutt, SL; Ransohoff, RM; Phares, TW; Stohlman, SA; Bergmann, CC;
Details: Publication Year 2011-07,Volume 85,Issue #13,Page 6136-6147
Journal Title: JOURNAL OF VIROLOGY
Publication Type: Journal Article
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.
Publisher: AMER SOC MICROBIOLOGY
Keywords: ANTIBODY-SECRETING CELLS; B-CELLS; MULTIPLE-SCLEROSIS; VIRUS ENCEPHALITIS; INFECTION; CXCR3; EXPRESSION; PERSISTENCE; CLEARANCE; MEMORY
Publisher's Version: https://doi.org/10.1128/JVI.00202-11
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2011-07-01 12:00:00