Immune-mediated pathogenesis and immune regulation during fatal alphavirus encephalomyelitis

alphavirus;Th17 cells;interleukin-10;encephalitis;Immunology

Kulcsar, KirstenZink, M. Christine ;

Johns Hopkins University

关键词: alphavirus;    Th17 cells;    interleukin-10;    encephalitis;    Immunology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/40655/KULCSAR-DISSERTATION-2014.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Encephalitic viral infections are emerging as an important cause of morbidity and mortality worldwide. The mechanisms by which these infections cause disease, however, are poorly understood.To better understand the pathogenesis of severe encephalitic viral infections, these studies focused on determining the mechanisms of immune-mediated pathogenesis and the regulation of this response during Neuroadapted Sindbis virus (NSV) infection.The first set of experiments characterized the role of the immunoregulatory cytokine, interlukin-10 (IL-10), during NSV infection.These experiments showed that IL-10 is important in regulating the Th17 response to NSV infection.The next set of experiments characterized the Th17 populations in WT and Il10-/- mice.The Th17 cells found in WT and IL-10 KO mice had a pathogenic phenotype.Furthermore, in the absence of IL-10 the Th17 cells had increased GM-CSF expression and there was an expansion of the pathogenic Th1/17 population.The last set of experiments identified which cell types produce IL-10, as well as which cells express the IL-10R in order to determine possible mechanisms of action for IL-10 regulation of the Th17 response during NSV infection.These studies contribute to understanding the mechanisms of immune-mediated pathogenesis and regulation during encephalitic viral infections and other inflammatory diseases in the central nervous system.