Mycobacterium tuberculosis Protein Rv3841 Activates Dendritic Cells and Contributes to a T Helper 1 Immune Response

The attenuated vaccine Mycobacterium bovis 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...

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Main Authors: Seunga Choi, Han-Gyu Choi, Ki-Won Shin, Yong Woo Back, Hye-Soo Park, Jae Hwi Lee, Hwa-Jung Kim
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2018/3525302
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author Seunga Choi
Han-Gyu Choi
Ki-Won Shin
Yong Woo Back
Hye-Soo Park
Jae Hwi Lee
Hwa-Jung Kim
author_facet Seunga Choi
Han-Gyu Choi
Ki-Won Shin
Yong Woo Back
Hye-Soo Park
Jae Hwi Lee
Hwa-Jung Kim
author_sort Seunga Choi
collection DOAJ
description The attenuated vaccine Mycobacterium bovis 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-κB 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 CD4+CD44highCD62Llow 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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spelling doaj-art-cc8a6dad489d468d9f590956a04bb4662025-02-03T05:54:03ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/35253023525302Mycobacterium tuberculosis Protein Rv3841 Activates Dendritic Cells and Contributes to a T Helper 1 Immune ResponseSeunga Choi0Han-Gyu Choi1Ki-Won Shin2Yong Woo Back3Hye-Soo Park4Jae Hwi Lee5Hwa-Jung Kim6Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of KoreaDepartment of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of KoreaDepartment of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of KoreaDepartment of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of KoreaDepartment of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of KoreaDepartment of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of KoreaDepartment of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of KoreaThe attenuated vaccine Mycobacterium bovis 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-κB 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 CD4+CD44highCD62Llow 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.http://dx.doi.org/10.1155/2018/3525302
spellingShingle Seunga Choi
Han-Gyu Choi
Ki-Won Shin
Yong Woo Back
Hye-Soo Park
Jae Hwi Lee
Hwa-Jung Kim
Mycobacterium tuberculosis Protein Rv3841 Activates Dendritic Cells and Contributes to a T Helper 1 Immune Response
Journal of Immunology Research
title Mycobacterium tuberculosis Protein Rv3841 Activates Dendritic Cells and Contributes to a T Helper 1 Immune Response
title_full Mycobacterium tuberculosis Protein Rv3841 Activates Dendritic Cells and Contributes to a T Helper 1 Immune Response
title_fullStr Mycobacterium tuberculosis Protein Rv3841 Activates Dendritic Cells and Contributes to a T Helper 1 Immune Response
title_full_unstemmed Mycobacterium tuberculosis Protein Rv3841 Activates Dendritic Cells and Contributes to a T Helper 1 Immune Response
title_short Mycobacterium tuberculosis Protein Rv3841 Activates Dendritic Cells and Contributes to a T Helper 1 Immune Response
title_sort mycobacterium tuberculosis protein rv3841 activates dendritic cells and contributes to a t helper 1 immune response
url http://dx.doi.org/10.1155/2018/3525302
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