Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice.
Invasion of the central nervous system (CNS) by African trypanosomes represents a critical step in the development of human African trypanosomiasis. In both clinical cases and experimental mouse infections it has been demonstrated that predisposition to CNS invasion is associated with a type 1 systemic inflammatory response. Using the Trypanosoma brucei brucei GVR35 experimental infection model, we demonstrate that systemic delivery of the counter-inflammatory cytokine IL-10 lowers plasma IFN-γ and TNF-α concentrations, CNS parasitosis and ameliorates neuro-inflammatory pathology and clinical symptoms of disease. The results provide evidence that CNS invasion may be susceptible to immunological attenuation.
Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Jean
J
Rodgers
Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Barbara
B
Bradley
Department of Neurology, Institute of Neurological Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Peter G E
PG
Kennedy
Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom.
Jeremy M
JM
Sternberg
D000818:Animals; D002490:Central Nervous System / Q000469:parasitology* / Q000473:pathology; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000008:administration & dosage*; D051379:Mice; D010949:Plasma / Q000737:chemistry; D016896:Treatment Outcome; D014346:Trypanosoma brucei brucei / Q000254:growth & development*; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma