Abstract
Tuberculosis (TB) caused by Mycobacterium tuberculosis constitutes an ongoing threat to global health. An antigen that can induce dendritic cell (DC) maturation and lead to enhanced cellular immunity is crucial to the development of an effective TB vaccine. Here, we investigated the functional roles and the related signaling mechanism of the Rv0577 protein, a M. tuberculosis complex-restricted secreted protein involved in the methylglyoxal detoxification pathway. Rv0577 recognizes Toll-like receptor 2 (TLR2) and functionally induces DC maturation by augmenting the expression of cell surface molecules (CD80, CD86, and MHC class I and II) and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IL-12p70) in DCs on MyD88-dependent signaling, mitogen-activated protein kinases, and nuclear factor κB signaling pathways. In addition, Rv0577-treated DCs activated naive T cells, effectively polarized CD4+ and CD8+ T cells to secrete IFN-γ and IL-2, and induced T-cell proliferation, indicating that this protein possibly contributes to Th1-polarization of the immune response. More important, unlike LPS, Rv0577-treated DCs specifically induced the proliferation of memory CD4+/CD8+CD44highCD62Llow T cells in the spleen of M. tuberculosis-infected mice in a TLR2-dependent manner. Taken together, these findings suggest that Rv0577 may regulate innate and adaptive immunity by interacting with TLR2, a finding that could be helpful in the design of new TB vaccines.
| Original language | English |
|---|---|
| Pages (from-to) | 2695-2711 |
| Number of pages | 17 |
| Journal | FASEB Journal |
| Volume | 26 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2012 Jun 1 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
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Mycobacterium tuberculosis Rv0577, a novel TLR2 agonist, induces maturation of dendritic cells and drives Th1 immune response. / Byun, Eui Hong; Kim, Woo Sik; Kim, Jong Seok; Jung, In Duk; Park, Yeong Min; Kim, Hwa Jung; Cho, Sangnae; Shin, SungJae.
In: FASEB Journal, Vol. 26, No. 6, 01.06.2012, p. 2695-2711.Research output: Contribution to journal › Article
TY - JOUR
T1 - Mycobacterium tuberculosis Rv0577, a novel TLR2 agonist, induces maturation of dendritic cells and drives Th1 immune response
AU - Byun, Eui Hong
AU - Kim, Woo Sik
AU - Kim, Jong Seok
AU - Jung, In Duk
AU - Park, Yeong Min
AU - Kim, Hwa Jung
AU - Cho, Sangnae
AU - Shin, SungJae
PY - 2012/6/1
Y1 - 2012/6/1
N2 - Tuberculosis (TB) caused by Mycobacterium tuberculosis constitutes an ongoing threat to global health. An antigen that can induce dendritic cell (DC) maturation and lead to enhanced cellular immunity is crucial to the development of an effective TB vaccine. Here, we investigated the functional roles and the related signaling mechanism of the Rv0577 protein, a M. tuberculosis complex-restricted secreted protein involved in the methylglyoxal detoxification pathway. Rv0577 recognizes Toll-like receptor 2 (TLR2) and functionally induces DC maturation by augmenting the expression of cell surface molecules (CD80, CD86, and MHC class I and II) and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IL-12p70) in DCs on MyD88-dependent signaling, mitogen-activated protein kinases, and nuclear factor κB signaling pathways. In addition, Rv0577-treated DCs activated naive T cells, effectively polarized CD4+ and CD8+ T cells to secrete IFN-γ and IL-2, and induced T-cell proliferation, indicating that this protein possibly contributes to Th1-polarization of the immune response. More important, unlike LPS, Rv0577-treated DCs specifically induced the proliferation of memory CD4+/CD8+CD44highCD62Llow T cells in the spleen of M. tuberculosis-infected mice in a TLR2-dependent manner. Taken together, these findings suggest that Rv0577 may regulate innate and adaptive immunity by interacting with TLR2, a finding that could be helpful in the design of new TB vaccines.
AB - Tuberculosis (TB) caused by Mycobacterium tuberculosis constitutes an ongoing threat to global health. An antigen that can induce dendritic cell (DC) maturation and lead to enhanced cellular immunity is crucial to the development of an effective TB vaccine. Here, we investigated the functional roles and the related signaling mechanism of the Rv0577 protein, a M. tuberculosis complex-restricted secreted protein involved in the methylglyoxal detoxification pathway. Rv0577 recognizes Toll-like receptor 2 (TLR2) and functionally induces DC maturation by augmenting the expression of cell surface molecules (CD80, CD86, and MHC class I and II) and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IL-12p70) in DCs on MyD88-dependent signaling, mitogen-activated protein kinases, and nuclear factor κB signaling pathways. In addition, Rv0577-treated DCs activated naive T cells, effectively polarized CD4+ and CD8+ T cells to secrete IFN-γ and IL-2, and induced T-cell proliferation, indicating that this protein possibly contributes to Th1-polarization of the immune response. More important, unlike LPS, Rv0577-treated DCs specifically induced the proliferation of memory CD4+/CD8+CD44highCD62Llow T cells in the spleen of M. tuberculosis-infected mice in a TLR2-dependent manner. Taken together, these findings suggest that Rv0577 may regulate innate and adaptive immunity by interacting with TLR2, a finding that could be helpful in the design of new TB vaccines.
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U2 - 10.1096/fj.11-199588
DO - 10.1096/fj.11-199588
M3 - Article
VL - 26
SP - 2695
EP - 2711
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 6
ER -