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Title: The mechanistic study on the role of dendritic cell in modulating immune response in infections and allergy
Authors: Gao, Xiaoling
Supervisor: Yang, Xi (Medical Microbiology)
Examining Committee: Uzonna, Jude (Immunology) Fowke, Keith (Medical Microbiology) Cao, Jingxin (Medical Microbiology)
Graduation Date: May 2011
Keywords: Allergy
Issue Date: 11-Apr-2011
Citation: Xiaoling Gao, Shuhe Wang, Yijun Fan et al, CD8+ DCs, but not CD8-DCs, isolated from BCG-infected mice reduce pathological reactions induced by mycobacterial challenge infection, PLoS One
Abstract: The study mainly focuses on the role of dendritic cells (DCs),especially DC subsets, in modulating intracellular bacterial infections and the modulating effect of these infections on allergic responses. Specifically, it investigated the molecular mechanisms of 1) mycobacterial infection, 2) chlamydia infection and 3) the effect of these infections on allergic reactions. The results demonstrated that Bacillus Calmette-Guérin (BCG) vaccination promoted the expansion of CD8+DCs, which showed a more mature phenotype and produced more IL-12 compared to CD8-DCs. In vivo BCG-primed CD8+DC, but not CD8-DC, was the dominant DC subset in inducing protective immunity against BCG infection. Further, the results showed that adoptive transfer of different DC subsets from BCG-infected mice inhibited OVA-induced allergic reactions through immune deviation and immune regulation mechanisms. In addition, the results showed that CD8+DCs primed by Chlamydia, another intracellular bacterial pathogen, inhibited the allergic responses through IL-10 dependent pathway. Further, the data demonstrated that IL-10 inhibited the expansion of protective Th17 cells following Chlamydia infection. DCs from IL-10 KO mice showed significantly higher ICOS ligand (ICOS-L) expression compared to WT mice. Th17 from Chlamydia infected mice, but not Th1 cells, expressed high levels of ICOS. Blockade of ICOS/ICOSL signaling virtually abolished the Th17 promoting effect of DCs from IL-10 KO mice but had no significant effect on Th1 cells. This study provided new knowledge on the immune regulation of DC, especially its subsets, which may be helpful for the rational development of new preventive or therapeutic methods to tuberculosis / Chlamydia infections and allergic diseases.
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