title: High production of CXCL13 in blood and brain during persistent infection with the relapsing fever spirochete Borrelia turicatae.
abstract: Relapsing fever (RF) is a multisystemic borrelial infection with frequent neurologic involvement referred to as neuroborreliosis. The absence of an effective antibody response results in persistent infection. To study the consequences to the brain of persistent infection with the RF spirochete Borrelia turicatae, we studied B cell (Igh6-/-) and B and T (Rag1-/-) cell-deficient mice inoculated with isogenic serotypes 1 (Bt1) or 2 (Bt2). We found that Bt1 was more tissue tropic than Bt2, not only for brain but also for heart. Igh6-/- mice developed more severe clinical disease than Rag1-/- mice. Bt1-infected brains had widespread microgliosis/brain macrophage activation despite localization of spirochetes in the leptomeninges rather than the brain parenchyma itself. Oligoarray analysis revealed that CXCL13 was the most upregulated gene in the brain of Bt1-infected Igh6-/- mice. CXCL13 was also the most abundant of the chemokines we measured in infected blood. Persistent infection did not result in injury to the brain. Treatment with exogenous interleukin-10 reduced microgliosis in the brain and production of CXCL13 in the blood. We concluded that brain involvement in B cell-deficient mice persistently infected with B. turicatae is characterized by prominent microgliosis and production of CXCL13 without detectable injury.
authors.affiliation: Department of Neurology and Neuroscience and Center for Emerging Pathogens, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Harald
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Diana
authors.initials: D
authors.lastname: Londoño
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Bai
authors.forename: Erik S
authors.initials: ES
authors.lastname: Cabral
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Quandt
authors.forename: Ron
authors.initials: R
authors.lastname: Hornung
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.forename: Adriana
authors.initials: A
authors.lastname: Marques
authors.forename: Diego
authors.initials: D
authors.lastname: Cadavid
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001898:Borrelia / Q000145:classification; D001899:Borrelia Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000382:microbiology; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006321:Heart / Q000382:microbiology; D016753:Interleukin-10 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D012061:Relapsing Fever / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric
chemical_list: D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D012333:RNA, Messenger; D016753:Interleukin-10