title: Induction of distinct neurologic disease manifestations during relapsing fever requires T lymphocytes.
abstract: Relapsing fever borreliosis is a multisystemic infection characterized primarily by bacteremia but can extend to the CNS. The incidence of CNS disease manifestations in humans depends on the infecting relapsing fever Borrelia species. In the murine model of Borrelia hermsii infection we found high incidence of distinct signs of CNS disease that ranged from a flaccid tail to complete paralysis of hind limbs. Infiltration of large number of T cells into the spinal cord of B. hermsii-infected mice and the upregulation of MHC class II and CD80 on infiltrating macrophages and on microglial cells suggested a role for T cell and Ag-presenting cell interactions in this pathogenesis. Indeed, B. hermsii infection did not induce CNS disease manifestations in T cell-deficient mice (TCR-beta x delta(-/-)), although it resulted in bacteremia comparable to wild-type (Wt) level. Moreover, the infiltration of immune cells into the spinal cord of TCR-beta x delta(-/-) mice was reduced and the resident microglial cells were not activated. Histopathological analysis of lumbar sections of the spinal cord confirmed severe inflammation in Wt but not in TCR-beta x delta(-/-) mice. Induction of CNS disease was dependent on the B. hermsii strain as well as on the ability of the host to control bacteremia. Mice that are impaired in controlling B. hermsii, such as CD14(-/-) mice, exhibited more severe CNS disease than Wt mice. This study demonstrates that distinct neurologic disease manifestations develop during relapsing fever and that T cells play a critical role in the induction of neuropathogenesis.
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Hongqi
authors.initials: H
authors.lastname: Liu
authors.forename: Denise
authors.initials: D
authors.lastname: Fitzgerald
authors.forename: Bruno
authors.initials: B
authors.lastname: Gran
authors.forename: John M
authors.initials: JM
authors.lastname: Leong
authors.forename: Kishore R
authors.initials: KR
authors.lastname: Alugupalli
mesh_terms: D000818:Animals; D001898:Borrelia / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D005260:Female; D007121:Immunocompetence / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010243:Paralysis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012061:Relapsing Fever / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D013116:Spinal Cord / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*