CpG-A stimulates Hsp72 secretion from plasmacytoid dendritic cells, facilitating cross-presentation

Tanaka, Tsutomu; Kajiwara, Toshimitsu; Kutomi, Goro; Kurotaki, Takehiro; Saito, Keita; Kanaseki, Takayuki; Tsukahara, Tomohide; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Hirata, Koichi; Okamoto, Yoshiharu; Sato, Noriyuki; Tamura, Yasuaki

doi:10.1016/j.imlet.2015.06.014

Immunology Letters

2015

DOI: 10.1016/j.imlet.2015.06.014

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CpG-A stimulates Hsp72 secretion from plasmacytoid dendritic cells, facilitating cross-presentation

Tsutomu Tanaka

Toshimitsu Kajiwara

Goro Kutomi

et al.

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Cited by 3 publications

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“…Other laboratories have also shown that pDC cross-presented antigens from Influenza A Virus (24)(25)(26)(27), tumors (22,23,28,29) or Cytomegalovirus (28) either as cell-associated antigens, long peptides, lipopeptides or particulate antigens. Similarly, murine pDC were also shown to be able to perform cross-presentation (30,31). In addition, pDC have exacerbated sensing properties and strong inflammatory responses, particularly the production of interferon (IFN)α, which has been shown to activate and increase CD8 + T cell function (32)(33)(34).…”

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confidence: 99%

Cell-Associated HIV Cross-Presentation by Plasmacytoid Dendritic Cells Is Potentiated by Noncognate CD8+ T Cell Preactivation

Isnard

Hatton

Iannetta

et al. 2021

The Journal of Immunology

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Human plasmacytoid dendritic cells (pDC) can cross-present antigens from apoptotic HIVinfected cells or tumor cells to CD8 + T cells. As pDC respond to HIV virions by maturing and secreting cytokines, we wondered whether these innate properties would affect crosspresentation from HIV-infected cells. We incubated purified blood DC with apoptotic HIVinfected H9 cells and then explored the activation process of HIV-specific cloned CD8 + T cells, in the presence of saquinavir We studied IFN-g secretion by HIV-specific T cells, which is known to be tightly regulated by engagement of the T cell receptor. We found that HIV-specific secretion by cloned HIV-specific CD8 + T cells was stimulated by pDC and cDC1 more than by cDC2, and was strictly MHC-Class I (MHC-I)-restricted. Surprisingly, intracellular production of IFN-γ was only partly MHC-I restricted for pDC, indicating a non-cognate CD8 + T cell activation. Plasmacytoid DC, but not cDC, matured and secreted IFN-a in the presence of apoptotic H9HIV cells. A cocktail of IFN-a, IFN-b and TNF-a induced intracellular production of IFN-γ but not Granzyme-B, mimicked the non-cognate mechanism, and neutralization of type I IFN signaling blocked non-cognate intracellular production of IFN-γ in the co-culture model. Moreover, cognate stimulation was required to induce IFN-γ secretion in addition to the cytokine cocktail. Thus, IFN-γ secretion is tightly regulated by engagement of the TCR as expected, but in the context of virus-infected cells, pDC can trigger intracellular IFN-γ accumulation in CD8 + T cells, potentializing IFN-γ secretion once CD8 + T cells make cognate interactions. These findings may help manipulate type I IFN signaling to enhance specifically antigen-specific CD8 + T cell activation against chronic infections or tumors. • HIV-infected H9 cells induce type I IFN production by pDC • Type I IFN induces IFN-γ but not Granzyme intracellular production in CD8 + T cells • pDC cross-present MHC-I-restricted HIV-Gag antigen to specific CD8 + T cells • IFN-γ secretion is potentiated by type I IFN, but only upon cognate interaction

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mentioning

confidence: 99%

Cell-Associated HIV Cross-Presentation by Plasmacytoid Dendritic Cells Is Potentiated by Noncognate CD8+ T Cell Preactivation

Isnard

Hatton

Iannetta

et al. 2021

The Journal of Immunology

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Systemic administration of polymersomal oncolytic peptide LTX-315 combining with CpG adjuvant and anti-PD-1 antibody boosts immunotherapy of melanoma

Xia

Wei

Zhao

et al. 2021

Journal of Controlled Release

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Exosomal HSP60: a potentially useful biomarker for diagnosis, assessing prognosis, and monitoring response to treatment

Bavisotto

Cappello

Macario

et al. 2017

Expert Review of Molecular Diagnostics

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Cell-to-cell communication is imperative for life and it is mediated by sending and receiving information via the secretion and subsequent receptor-mediated detection of biological molecules. Exosomes (EXs) secreted from cells to the extracellular environment play an important role in intercellular communication in normal and pathological conditions. Areas covered: New evidence indicates that tumor cells-derived EXs contribute to cancer progression through the modulation of tumor microenvironment. The exosomal heat shock protein 60 (HSP60) is very likely a key player in intercellular cross-talk, particularly during the progress of diseases, such as cancer. Many studies have focused on the extracellular roles played by HSP60 that pertain to cancer development and immune system stimulation. Our experimental data in vitro and in vivo demonstrated that HSP60 occurs on the surface of EXs secreted by tumour cells. Expert commentary: Exosomal HSP60 has great potential for clinical applications, as a 'liquid biopsy', including its use as biomarker for diagnostics, assessing prognosis, and monitoring disease progression and response to treatment, particularly in cancer.

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CpG-A stimulates Hsp72 secretion from plasmacytoid dendritic cells, facilitating cross-presentation

Cited by 3 publications

References 16 publications

Cell-Associated HIV Cross-Presentation by Plasmacytoid Dendritic Cells Is Potentiated by Noncognate CD8+ T Cell Preactivation

Cell-Associated HIV Cross-Presentation by Plasmacytoid Dendritic Cells Is Potentiated by Noncognate CD8+ T Cell Preactivation

Systemic administration of polymersomal oncolytic peptide LTX-315 combining with CpG adjuvant and anti-PD-1 antibody boosts immunotherapy of melanoma

Exosomal HSP60: a potentially useful biomarker for diagnosis, assessing prognosis, and monitoring response to treatment

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