Mycobacterium tuberculosis RpfE promotes simultaneous Th1- and Th17-type T-cell immunity via TLR4-dependent maturation of dendritic cells

Han Gyu Choi, Woo Sik Kim, Yong Woo Back, Hongmin Kim, Kee Woong Kwon, Jong Seok Kim, SungJae Shin, Hwa Jung Kim

Research output: Contribution to journalArticle

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Abstract

Reciprocal induction of the Th1 and Th17 immune responses is essential for optimal protection against Mycobacterium tuberculosis (Mtb); however, only a few Mtb antigens are known to fulfill this task. A functional role for resuscitation-promoting factor (Rpf) E, a latency-associated member of the Rpf family, in promoting naïve CD4+ T-cell differentiation toward both Th1 and Th17 cell fates through interaction with dendritic cells (DCs) was identified in this study. RpfE induces DC maturation by increasing expression of surface molecules and the production of IL-6, IL-1β, IL-23p19, IL-12p70, and TNF-α but not IL-10. This induction is mediated through TLR4 binding and subsequent activation of ERK, p38 MAPKs, and NF-κB signaling. RpfE-treated DCs effectively caused naïve CD4+ T cells to secrete IFN-γ, IL-2, and IL-17A, which resulted in reciprocal expansions of the Th1 and Th17 cell response along with activation of T-bet and RORγt but not GATA-3. Furthermore, lung and spleen cells from Mtb-infected WT mice but not from TLR4-/- mice exhibited Th1 and Th17 polarization upon RpfE stimulation. Taken together, our data suggest that RpfE has the potential to be an effective Mtb vaccine because of its ability to activate DCs that simultaneously induce both Th1- and Th17-polarized T-cell expansion.

Original languageEnglish
Pages (from-to)1957-1971
Number of pages15
JournalEuropean Journal of Immunology
Volume45
Issue number7
DOIs
Publication statusPublished - 2015 Jul 1

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Th17 Cells
Mycobacterium tuberculosis
Dendritic Cells
Immunity
T-Lymphocytes
Th1 Cells
Resuscitation
Interleukin-23 Subunit p19
Tuberculosis Vaccines
Interleukin-17
p38 Mitogen-Activated Protein Kinases
Interleukin-1
Interleukin-10
Interleukin-2
Cell Differentiation
Interleukin-6
Spleen
Lung

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Choi, Han Gyu ; Kim, Woo Sik ; Back, Yong Woo ; Kim, Hongmin ; Kwon, Kee Woong ; Kim, Jong Seok ; Shin, SungJae ; Kim, Hwa Jung. / Mycobacterium tuberculosis RpfE promotes simultaneous Th1- and Th17-type T-cell immunity via TLR4-dependent maturation of dendritic cells. In: European Journal of Immunology. 2015 ; Vol. 45, No. 7. pp. 1957-1971.
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abstract = "Reciprocal induction of the Th1 and Th17 immune responses is essential for optimal protection against Mycobacterium tuberculosis (Mtb); however, only a few Mtb antigens are known to fulfill this task. A functional role for resuscitation-promoting factor (Rpf) E, a latency-associated member of the Rpf family, in promoting na{\"i}ve CD4+ T-cell differentiation toward both Th1 and Th17 cell fates through interaction with dendritic cells (DCs) was identified in this study. RpfE induces DC maturation by increasing expression of surface molecules and the production of IL-6, IL-1β, IL-23p19, IL-12p70, and TNF-α but not IL-10. This induction is mediated through TLR4 binding and subsequent activation of ERK, p38 MAPKs, and NF-κB signaling. RpfE-treated DCs effectively caused na{\"i}ve CD4+ T cells to secrete IFN-γ, IL-2, and IL-17A, which resulted in reciprocal expansions of the Th1 and Th17 cell response along with activation of T-bet and RORγt but not GATA-3. Furthermore, lung and spleen cells from Mtb-infected WT mice but not from TLR4-/- mice exhibited Th1 and Th17 polarization upon RpfE stimulation. Taken together, our data suggest that RpfE has the potential to be an effective Mtb vaccine because of its ability to activate DCs that simultaneously induce both Th1- and Th17-polarized T-cell expansion.",
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Mycobacterium tuberculosis RpfE promotes simultaneous Th1- and Th17-type T-cell immunity via TLR4-dependent maturation of dendritic cells. / Choi, Han Gyu; Kim, Woo Sik; Back, Yong Woo; Kim, Hongmin; Kwon, Kee Woong; Kim, Jong Seok; Shin, SungJae; Kim, Hwa Jung.

In: European Journal of Immunology, Vol. 45, No. 7, 01.07.2015, p. 1957-1971.

Research output: Contribution to journalArticle

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AU - Choi, Han Gyu

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AB - Reciprocal induction of the Th1 and Th17 immune responses is essential for optimal protection against Mycobacterium tuberculosis (Mtb); however, only a few Mtb antigens are known to fulfill this task. A functional role for resuscitation-promoting factor (Rpf) E, a latency-associated member of the Rpf family, in promoting naïve CD4+ T-cell differentiation toward both Th1 and Th17 cell fates through interaction with dendritic cells (DCs) was identified in this study. RpfE induces DC maturation by increasing expression of surface molecules and the production of IL-6, IL-1β, IL-23p19, IL-12p70, and TNF-α but not IL-10. This induction is mediated through TLR4 binding and subsequent activation of ERK, p38 MAPKs, and NF-κB signaling. RpfE-treated DCs effectively caused naïve CD4+ T cells to secrete IFN-γ, IL-2, and IL-17A, which resulted in reciprocal expansions of the Th1 and Th17 cell response along with activation of T-bet and RORγt but not GATA-3. Furthermore, lung and spleen cells from Mtb-infected WT mice but not from TLR4-/- mice exhibited Th1 and Th17 polarization upon RpfE stimulation. Taken together, our data suggest that RpfE has the potential to be an effective Mtb vaccine because of its ability to activate DCs that simultaneously induce both Th1- and Th17-polarized T-cell expansion.

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