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Monocyte-derived dendritic cells early exposed to Mycobacterium tuberculosis induce an enhanced T helper 17 response and transfer mycobacterial antigens
Abstract Tuberculosis (TB) is a complex disease, and the success of the bacterium depends on its ability to evade the immune response. Previously, we determined that Mycobacterium tuberculosis ( Mtb ) impairs the function of dendritic cells (DC), promoting the generation of cells that are poor stimu...
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Published in: | International journal of medical microbiology 2016-11, Vol.306 (7), p.541-553 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Abstract Tuberculosis (TB) is a complex disease, and the success of the bacterium depends on its ability to evade the immune response. Previously, we determined that Mycobacterium tuberculosis ( Mtb ) impairs the function of dendritic cells (DC), promoting the generation of cells that are poor stimulators of mycobacterial antigen-specific CD4T cells, which are required to control this persistent infection. In this study, we aimed to determine the mechanisms by which monocyte-derived DCs differentiated in the presence of Mtb ( Mtb DC) may impact on the proliferation of specific anti-mycobacterial T cells. We found that the presence of Mtb during monocyte-derived DC differentiation favours T helper (Th) 2 and Th17 polarization, in detriment of a Th1 response, compared to DC mature with Mtb . The bias on T cell polarization was associated to the profile of C-type lectin receptors expression found in Mtb DC (DC-SIGNlow /MRlow /Dectin-1high ). Alternatively, Mtb DC release Mtb antigens (Ag) that can be taken up and presented by bystander DC, promoting the proliferation of CD4T cells, but to a lesser extent than direct presentation by Mtb -matured DC. In summary, we have further characterized the generation of Mtb DC as an effective evasion strategy driven by the pathogen, leading to the inhibition of Ag-presentation and bias of T cell polarization towards Th2 and Th17 profiles, features which partially explain the persistence of Mtb in the host. |
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ISSN: | 1438-4221 1618-0607 |
DOI: | 10.1016/j.ijmm.2016.06.004 |