The attenuated vaccine BCG (Bacille Calmette Guerin) has limited protective efficacy against TB. The development of more effective TB vaccines has focused on the mycobacterial antigens that cause strong T helper 1 (Th1) responses. Mtb protein Rv3841 (bacterioferritin B; BfrB) is known to play a crucial role in the growth of Mtb. Nonetheless, it is unclear whether Rv3841 can induce protective immunity against Mtb. Here, we studied the action of Rv3841 in maturation of dendritic cells (DCs) and its engagement in the development of T-cell immunity. We found that Rv3841 functionally activated DCs by upregulating costimulatory molecules and increased secretion of proinflammatory cytokines. Activation of DCs by Rv3841 was mediated by Toll-like receptor 4 (TLR4), followed by triggering of mitogen-activated protein kinase and nuclear factor-B signaling pathways. In addition, Rv3841-matured DCs effectively proliferated and polarized Th1 immune response of naïve CD4 and CD8 T-cells. Moreover, Rv3841 specifically caused the expansion of CD4CD44CD62L T-cells from Mtb-infected mice; besides, the T-cells activated by Rv3841-matured DCs inhibited intracellular mycobacterial growth. Our data suggest that Rv3841 induces DC maturation and protective immune responses, a finding that may provide candidate of effective TB vaccines.
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http://dx.doi.org/10.1155/2018/3525302 | DOI Listing |
Curr Protein Pept Sci
November 2024
Department of Biochemistry, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra (UP)-282001, India.
Introduction: The rising prevalence of Mycobacterium tuberculosis (M.tb) strains resistant to aminoglycosides (amikacin and kanamycin) challenges effective TB control and treatment. Understanding the mechanisms behind this resistance is crucial since aminoglycosides are a mainstay of TB therapy.
View Article and Find Full Text PDFFront Immunol
June 2021
Department of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong Unviersity School of Medicine, Shanghai, China.
Long-term immunoreactivity to mycobacterial antigens in Bovis Calmette-Guérin (BCG)-vaccinated population is not well investigated. Herein, 361 volunteer healthy donors (HDs) with neonatal BCG vaccination from Shanghai region (China) were enrolled. They were subdivided into ESAT-6/CFP10 (E6C10) and ESAT-6/CFP10 (E6C10) groups based on gamma-interferon release assays (IGRAs).
View Article and Find Full Text PDFPLoS One
August 2020
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, United States of America.
Better triage tests for screening tuberculosis (TB) disease are needed for people living with HIV (PLHIV). We performed the first evaluation of a previously-validated 8-antigen serological panel to screen PLHIV for pulmonary TB in Kampala, Uganda. We selected a random 1:1 sample with and without TB (defined by sputum culture) from a cohort of PLHIV initiating antiretroviral therapy.
View Article and Find Full Text PDFFront Microbiol
June 2018
Tropical Institute of Pathology and Public Health, Department of Microbiology, Immunology, Parasitology and Pathology, Federal University of Goiás, Goiânia, Brazil.
complex has been characterized in the last decade as part of a cluster of mycobacteria that evolved from an opportunistic to true human pathogen; however, the factors responsible for pathogenicity are still undefined. It appears that the success of mycobacterial infection is intrinsically related with the capacity of the bacteria to regulate intracellular iron levels, mostly using iron storage proteins. This study evaluated two potential subsp.
View Article and Find Full Text PDFJ Immunol Res
September 2018
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
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