Interleukin 10 protects the brain microcirculation from spirochetal injury.
Spirochetal infections are an important cause of neurological disease. In previous studies of the pathogenesis of spirochetal brain infection, mice inoculated with Borrelia turicatae, an agent of tick-borne relapsing fever in North America, developed mild meningitis and parenchymal activation/infiltration by interleukin 10 (IL-10)-producing microglia/macrophages. Here, we investigated the neuroprotective effects of IL-10 during spirochetal infection by comparing the outcomes of B. turicatae infection in wild-type and IL-10-deficient RAG2-deficient mice. Mice were infected with either serotype 1 (Bt1), which causes more brain infection but lower bacteremia, or Bt2, which causes less brain infection but higher bacteremia. Interleukin 10 deficiency resulted in early death from subarachnoid/intraparenchymal brain hemorrhage in Bt2-infected mice. These mice had marked apoptosis of brain microvascular endothelial cells as assessed by terminal transferase-mediated DNA nick end-labeling staining. In contrast, Bt1 infection caused milder subarachnoid hemorrhage. Neuronal apoptosis was observed in mice infected with both serotypes and was prominent in the cerebellum. Neutralization of tumor necrosis factor prevented death and reduced morbidity and brain injury in mice infected by both serotypes. We conclude that IL-10 plays a critical role protecting the cerebral microcirculation from spirochetal injury possibly by inhibition effects of tumor necrosis factor.
Londoño
Diana
D
Department of Neurology and Neuroscience and Center for Emerging Pathogens at UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
Carvajal
Jenny
J
Arguelles-Grande
Carolina
C
Marques
Adriana
A
Cadavid
Diego
D
D000818:Animals; D001899:Borrelia Infections / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control*; D001921:Brain / Q000473:pathology*; D004396:Coloring Agents; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006470:Hemorrhage / Q000209:etiology / Q000473:pathology; D020287:In Situ Nick-End Labeling; D016753:Interleukin-10 / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000079424:Tumor Necrosis Factor Inhibitors
D004396:Coloring Agents; D016207:Cytokines; D000079424:Tumor Necrosis Factor Inhibitors; D016753:Interleukin-10
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