Abstract
A gradual understanding of the proline-glutamate (PE) and proline-proline-glutamate (PPE) families, which compromise 10% of the coding regions in the Mycobacterium tuberculosis (Mtb) genome, has uncovered unique roles in host–pathogen interactions. However, the immunological function of PE27 (Rv2769c), the largest PE member, remains unclear. Here, we explored the functional roles and related signaling mechanisms of PE27 in the interaction with dendritic cells (DCs) to shape the T cell response. PE27 phenotypically and functionally induces DC maturation by up-regulating CD80, CD86, MHC class I and MHC class II expression on the DC surface to promote the production of TNF-α, IL-1β, IL-6, and IL-12p70 but not IL-10. Additionally, we found that PE27-mediated DC activation requires the participation of mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) signaling pathways. Interestingly, PE27-treated DCs directed naïve CD4+ T cells to secrete IFN-γ and activate T-bet but not GATA-3. PE27 also induced IFN-γ-producing memory T cell responses in Mtb-infected mice, indicating that PE27 contributes to Th1-polarization. Taken together, these findings suggest that PE27 possesses Th1-polarizing potential through DC maturation and could be useful in the design of TB vaccines.
| Original language | English |
|---|---|
| Pages (from-to) | 440-453 |
| Number of pages | 14 |
| Journal | Immunobiology |
| Volume | 221 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2016 Mar 1 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
- Hematology
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Mycobacterium tuberculosis PE27 activates dendritic cells and contributes to Th1-polarized memory immune responses during in vivo infection. / Kim, Woo Sik; Kim, Jong Seok; Cha, Seung Bin; Kim, So Jeong; Kim, Hongmin; Kwon, Kee Woong; Han, Seung Jung; Choi, Soo Young; Shin, SungJae.
In: Immunobiology, Vol. 221, No. 3, 01.03.2016, p. 440-453.Research output: Contribution to journal › Article
TY - JOUR
T1 - Mycobacterium tuberculosis PE27 activates dendritic cells and contributes to Th1-polarized memory immune responses during in vivo infection
AU - Kim, Woo Sik
AU - Kim, Jong Seok
AU - Cha, Seung Bin
AU - Kim, So Jeong
AU - Kim, Hongmin
AU - Kwon, Kee Woong
AU - Han, Seung Jung
AU - Choi, Soo Young
AU - Shin, SungJae
PY - 2016/3/1
Y1 - 2016/3/1
N2 - A gradual understanding of the proline-glutamate (PE) and proline-proline-glutamate (PPE) families, which compromise 10% of the coding regions in the Mycobacterium tuberculosis (Mtb) genome, has uncovered unique roles in host–pathogen interactions. However, the immunological function of PE27 (Rv2769c), the largest PE member, remains unclear. Here, we explored the functional roles and related signaling mechanisms of PE27 in the interaction with dendritic cells (DCs) to shape the T cell response. PE27 phenotypically and functionally induces DC maturation by up-regulating CD80, CD86, MHC class I and MHC class II expression on the DC surface to promote the production of TNF-α, IL-1β, IL-6, and IL-12p70 but not IL-10. Additionally, we found that PE27-mediated DC activation requires the participation of mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) signaling pathways. Interestingly, PE27-treated DCs directed naïve CD4+ T cells to secrete IFN-γ and activate T-bet but not GATA-3. PE27 also induced IFN-γ-producing memory T cell responses in Mtb-infected mice, indicating that PE27 contributes to Th1-polarization. Taken together, these findings suggest that PE27 possesses Th1-polarizing potential through DC maturation and could be useful in the design of TB vaccines.
AB - A gradual understanding of the proline-glutamate (PE) and proline-proline-glutamate (PPE) families, which compromise 10% of the coding regions in the Mycobacterium tuberculosis (Mtb) genome, has uncovered unique roles in host–pathogen interactions. However, the immunological function of PE27 (Rv2769c), the largest PE member, remains unclear. Here, we explored the functional roles and related signaling mechanisms of PE27 in the interaction with dendritic cells (DCs) to shape the T cell response. PE27 phenotypically and functionally induces DC maturation by up-regulating CD80, CD86, MHC class I and MHC class II expression on the DC surface to promote the production of TNF-α, IL-1β, IL-6, and IL-12p70 but not IL-10. Additionally, we found that PE27-mediated DC activation requires the participation of mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) signaling pathways. Interestingly, PE27-treated DCs directed naïve CD4+ T cells to secrete IFN-γ and activate T-bet but not GATA-3. PE27 also induced IFN-γ-producing memory T cell responses in Mtb-infected mice, indicating that PE27 contributes to Th1-polarization. Taken together, these findings suggest that PE27 possesses Th1-polarizing potential through DC maturation and could be useful in the design of TB vaccines.
UR - http://www.scopus.com/inward/record.url?scp=84957818481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84957818481&partnerID=8YFLogxK
U2 - 10.1016/j.imbio.2015.11.006
DO - 10.1016/j.imbio.2015.11.006
M3 - Article
C2 - 26655143
AN - SCOPUS:84957818481
VL - 221
SP - 440
EP - 453
JO - Immunobiology
JF - Immunobiology
SN - 0171-2985
IS - 3
ER -