Identification of Mycobacterial Ribosomal Proteins as Targets for CD4 + T Cells That Enhance Protective Immunity in Tuberculosis
| Autor: | Jiayong Xu, Scott J. Garforth, Steven A. Porcelli, Cecilia S. Lindestam Arlehamn, Steven C. Almo, William R. Jacobs, Steven C. Kennedy, Alessandro Sette, Sushma Bharrhan, John Chan, Alison J. Johnson |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mycobacterium bovis Tuberculosis T cell 030106 microbiology Immunology Biology Ribosomal RNA medicine.disease biology.organism_classification Microbiology Epitope Mycobacterium tuberculosis 03 medical and health sciences 030104 developmental biology Infectious Diseases medicine.anatomical_structure Ribosomal protein medicine Parasitology Tuberculosis vaccines |
| Zdroj: | Infection and Immunity. 86 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Mycobacterium tuberculosis remains a threat to global health, and a more efficacious vaccine is needed to prevent disease caused by M. tuberculosis We previously reported that the mycobacterial ribosome is a major target of CD4+ T cells in mice immunized with a genetically modified Mycobacterium smegmatis strain (IKEPLUS) but not in mice immunized with Mycobacterium bovis BCG. Two specific ribosomal proteins, RplJ and RpsA, were identified as cross-reactive targets of M. tuberculosis, but the breadth of the CD4+ T cell response to M. tuberculosis ribosomes was not determined. In the present study, a library of M. tuberculosis ribosomal proteins and in silico-predicted peptide libraries were used to screen CD4+ T cell responses in IKEPLUS-immunized mice. This identified 24 out of 57 M. tuberculosis ribosomal proteins distributed over both large and small ribosome subunits as specific CD4+ T cell targets. Although BCG did not induce detectable responses against ribosomal proteins or peptide epitopes, the M. tuberculosis ribosomal protein RplJ produced a robust and multifunctional Th1-like CD4+ T cell population when administered as a booster vaccine to previously BCG-primed mice. Boosting of BCG-primed immunity with the M. tuberculosis RplJ protein led to significantly reduced lung pathology compared to that in BCG-immunized animals and reductions in the bacterial burdens in the mediastinal lymph node compared to those in naive and standard BCG-vaccinated mice. These results identify the mycobacterial ribosome as a potential source of cryptic or subdominant antigenic targets of protective CD4+ T cell responses and suggest that supplementing BCG with ribosomal antigens may enhance protective vaccination against M. tuberculosis. |
| Databáze: | OpenAIRE |
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