title: Role of interleukin 10 during persistent infection with the relapsing fever Spirochete Borrelia turicatae.
abstract: Relapsing fever is an infection characterized by peaks of spirochetemia attributable to antibody selection against variable serotypes. In the absence of B cells, serotypes cannot be cleared, resulting in persistent infection. We previously identified differences in spirochetemia and disease severity during persistent infection of severe combined immunodeficiency mice with isogenic serotypes 1 (Bt1) or 2 (Bt2) of Borrelia turicatae. To investigate this further, we studied pathogen load, clinical disease, cytokine/chemokine production, and inflammation in mice deficient in B (Igh6-/-) or B and T (Rag1-/-) cells persistently infected with Bt1 or Bt2. The results showed that Igh6-/- mice, despite lower spirochetemia, had a significantly aggravated disease course compared with Rag1-/- mice. Measurement of cytokines revealed a significant positive correlation between pathogen load and interleukin (IL)-10 in blood, brain, and heart. Bt2-infected Rag1-/- mice harbored the highest spirochetemia and, at the same time, displayed the highest IL-10 plasma levels. In the brain, Bt1, which was five times more neurotropic than Bt2, caused higher IL-10 production. Activated microglia were the main source of IL-10 in brain. IL-10 injected systemically reduced disease and spirochetemia. The results suggest IL-10 plays a protective role as a down-regulator of inflammation and pathogen load during infection with relapsing fever spirochetes.
authors.affiliation: Cellular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Clinical Studies Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Harald
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Jens
authors.initials: J
authors.lastname: Schmidt
authors.forename: Diana
authors.initials: D
authors.lastname: Londoño
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Bai
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Quandt
authors.forename: Ron
authors.initials: R
authors.lastname: Hornung
authors.forename: Adriana
authors.initials: A
authors.lastname: Marques
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.forename: Diego
authors.initials: D
authors.lastname: Cadavid
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001898:Borrelia; D001899:Borrelia Infections / Q000276:immunology*; D018450:Disease Progression; D015536:Down-Regulation; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007249:Inflammation; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice; D012061:Relapsing Fever / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016753:Interleukin-10