Role of interleukin 10 during persistent infection with the relapsing fever Spirochete Borrelia turicatae.
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.
Gelderblom
Harald
H
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.
Schmidt
Jens
J
Londoño
Diana
D
Bai
Yunhong
Y
Quandt
Jacqueline
J
Hornung
Ron
R
Marques
Adriana
A
Martin
Roland
R
Cadavid
Diego
D
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*
D016753:Interleukin-10