دورية أكاديمية

Suboptimal Antigen Presentation Contributes to Virulence of Mycobacterium tuberculosis In Vivo

التفاصيل البيبلوغرافية
العنوان: Suboptimal Antigen Presentation Contributes to Virulence of Mycobacterium tuberculosis In Vivo
المؤلفون: Grace, Patricia S, Ernst, Joel D
المصدر: The Journal of Immunology, vol 196, iss 1
بيانات النشر: eScholarship, University of California
سنة النشر: 2016
المجموعة: University of California: eScholarship
مصطلحات موضوعية: Rare Diseases, Tuberculosis Vaccine, Vaccine Related, Infectious Diseases, Tuberculosis, HIV/AIDS, Prevention, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Aetiology, Infection, Good Health and Well Being, Acyltransferases, Animals, Antigen Presentation, Antigens, Bacterial, Bacterial Proteins, Cell Proliferation, Dendritic Cells, Lung, Lymphocyte Activation, Macrophages, Mice, Inbred C57BL, Knockout, Mycobacterium bovis, Mycobacterium tuberculosis, Th1 Cells, Pulmonary
جغرافية الموضوع: 357 - 364
الوصف: Mycobacterium tuberculosis commonly causes persistent or chronic infection, despite the development of Ag-specific CD4 T cell responses. We hypothesized that M. tuberculosis evades elimination by CD4 T cell responses by manipulating MHC class II Ag presentation and CD4 T cell activation and tested this hypothesis by comparing activation of Ag85B-specific CD4 T cell responses to M. tuberculosis and M. bovis bacillus Calmette-Guérin (BCG) Pasteur in vivo and in vitro. We found that, although M. tuberculosis persists in lungs of immunocompetent mice, M. bovis BCG is cleared, and clearance is T cell dependent. We further discovered that M. tuberculosis-infected macrophages and dendritic cells activate Ag85B-specific CD4 T cells less efficiently and less effectively than do BCG-infected cells, in vivo and in vitro, despite higher production and secretion of Ag85B by M. tuberculosis. During BCG infection, activation of Ag85B-specific CD4 T cells requires fewer infected dendritic cells and fewer Ag-producing bacteria than during M. tuberculosis infection. When dendritic cells containing equivalent numbers of M. tuberculosis or BCG were transferred to mice, BCG-infected cells activated proliferation of more Ag85B-specific CD4 T cells than did M. tuberculosis-infected cells. Differences in Ag85B-specific CD4 T cell activation were attributable to differential Ag presentation rather than differential expression of costimulatory or inhibitory molecules. These data indicate that suboptimal Ag presentation contributes to persistent infection and that limiting Ag presentation is a virulence property of M. tuberculosis.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: unknown
العلاقة: qt8td3w5jn; https://escholarship.org/uc/item/8td3w5jnTest
الإتاحة: https://escholarship.org/uc/item/8td3w5jnTest
حقوق: public
رقم الانضمام: edsbas.F84D2525
قاعدة البيانات: BASE