PPE39 of the mycobacterium tuberculosis strain Beijing/K induces Th1-cell polarization through dendritic cell maturation

Hong Hee Choi, Kee Woong Kwon, Seung Jung Han, Soon Myung Kang, Eunsol Choi, Ahreum Kim, Sang Nae Cho, Sung Jae Shin

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14 Citations (Scopus)


In a previous study, we have identified MTBK_24820, the complete protein form of PPE39 in the hypervirulent Mycobacterium tuberculosis (Mtb) strain Beijing/K by using comparative genomic analysis. PPE39 exhibited vaccine potential against Mtb challenge in a murine model. Thus, in this present study, we characterize PPE39-induced immunological features by investigating the interaction of PPE39 with dendritic cells (DCs). PPE39-treated DCs display reduced dextran uptake and enhanced MHC-I, MHC-II, CD80 and CD86 expression, indicating that this PPE protein induces phenotypic DC maturation. In addition, PPE39-treated DCs produce TNF-α, IL-6 and IL-12p70 to a similar and/or greater extent than lipopolysaccharide-treated DCs in a dose-dependent manner. The activating effect of PPE39 on DCs was mediated by TLR4 through downstream MAPK and NF-κB signaling pathways. Moreover, PPE39-treated DCs promoted naïve CD4+ T-cell proliferation accompanied by remarkable increases of IFN-γ and IL-2 secretion levels, and an increase in the Th1-related transcription factor T-bet but not in Th2-associated expression of GATA-3, suggesting that PPE39 induces Th1-type T-cell responses through DC activation. Collectively, the results indicate that the complete form of PPE39 is a so-far-unknown TLR4 agonist that induces Th1-cell biased immune responses by interacting with DCs.

Original languageEnglish
Article number228700
JournalJournal of cell science
Issue number17
Publication statusPublished - 2019

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2016R1A2A1A05005263 and NRF-2019R1A2C2003204) and by a grant from the Korean Health Technology R&D Project of the Ministry of Health and Welfare (HI17C0175), Republic of Korea.

Publisher Copyright:
© 2019. Published by The Company of Biologists Ltd

All Science Journal Classification (ASJC) codes

  • Cell Biology


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