کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8485266 | 1551708 | 2016 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Influence of phthiocerol dimycocerosate on CD4+ T cell priming and persistence during Mycobacterium tuberculosis infection
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
میکروبیولوژی و بیوتکنولوژی کاربردی
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چکیده انگلیسی
The characterisation of mycobacterial factors that influence or modulate the host immune response may aid the development of more efficacious TB vaccines. We have previously reported that Mycobacterium tuberculosis deficient in export of Phthiocerol Dimycocerosates (DIM) (MT103ÎdrrC) is more attenuated than wild type M. tuberculosis and provides sustained protective immunity compared to the existing BCG vaccine. Here we sought to define the correlates of immunity associated with DIM deficiency by assessing the impact of MT103ÎdrrC delivery on antigen presenting cell (APC) function and the generation of CD4+ T cell antigen-specific immunity. MT103ÎdrrC was a potent activator of bone marrow derived dendritic cells, inducing significantly greater expression of CD86 and IL-12p40 compared to BCG or the MT103 parental strain. This translated to an increased ability to initiate early in vivo priming of antigen-specific CD4+ T cells compared to BCG with enhanced release of IFN-γ and TNF upon antigen-restimulation. The heightened immunity induced by MT103ÎdrrC correlated with greater persistence within the spleen compared to BCG, however both MT103ÎdrrC and BCG were undetectable in the lung at 70 days post-vaccination. In immunodeficient RAG â/â mice, MT103ÎdrrC was less virulent than the parental MT103 strain, yet MT103ÎdrrC infected mice succumbed more rapidly compared to BCG-infected animals. These results suggest that DIM translocation plays a role in APC stimulation and CD4+ T cell activation during M. tuberculosis infection and highlights the potential of DIM-deficient strains as novel TB vaccine candidates.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Tuberculosis - Volume 99, July 2016, Pages 25-30
Journal: Tuberculosis - Volume 99, July 2016, Pages 25-30
نویسندگان
Rachel Pinto, Jonathan K. Nambiar, Lisa Leotta, Claudio Counoupas, Warwick J. Britton, James A. Triccas,