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RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production. / Sprokholt, Joris K.; Kaptein, Tanja M.; van Hamme, John L. et al.

In: PLoS pathogens, Vol. 13, No. 11, 2017, p. e1006738.

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@article{fa7d2162421e461cb0fe6e74eab3c5f6,
title = "RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production",
abstract = "Follicular T helper cells (TFH) are fundamental in orchestrating effective antibody-mediated responses critical for immunity against viral infections and effective vaccines. However, it is unclear how virus infection leads to TFH induction. We here show that dengue virus (DENV) infection of human dendritic cells (DCs) drives TFH formation via crosstalk of RIG-I-like receptor (RLR) RIG-I and MDA5 with type I Interferon (IFN) signaling. DENV infection leads to RLR-dependent IKKε activation, which phosphorylates IFNα/β receptor-induced STAT1 to drive IL-27 production via the transcriptional complex ISGF3. Inhibiting RLR activation as well as neutralizing antibodies against IL-27 prevented TFH formation. DENV-induced CXCR5+PD-1+Bcl-6+ TFH cells secreted IL-21 and activated B cells to produce IgM and IgG. Notably, RLR activation by synthetic ligands also induced IL-27 secretion and TFH polarization. These results identify an innate mechanism by which antibodies develop during viral disease and identify RLR ligands as potent adjuvants for TFH-promoting vaccination strategies",
author = "Sprokholt, {Joris K.} and Kaptein, {Tanja M.} and {van Hamme}, {John L.} and Overmars, {Ronald J.} and Gringhuis, {Sonja I.} and Geijtenbeek, {Teunis B. H.}",
year = "2017",
doi = "10.1371/journal.ppat.1006738",
language = "English",
volume = "13",
pages = "e1006738",
journal = "PLoS pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "11",

}

RIS

TY - JOUR

T1 - RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production

AU - Sprokholt, Joris K.

AU - Kaptein, Tanja M.

AU - van Hamme, John L.

AU - Overmars, Ronald J.

AU - Gringhuis, Sonja I.

AU - Geijtenbeek, Teunis B. H.

PY - 2017

Y1 - 2017

N2 - Follicular T helper cells (TFH) are fundamental in orchestrating effective antibody-mediated responses critical for immunity against viral infections and effective vaccines. However, it is unclear how virus infection leads to TFH induction. We here show that dengue virus (DENV) infection of human dendritic cells (DCs) drives TFH formation via crosstalk of RIG-I-like receptor (RLR) RIG-I and MDA5 with type I Interferon (IFN) signaling. DENV infection leads to RLR-dependent IKKε activation, which phosphorylates IFNα/β receptor-induced STAT1 to drive IL-27 production via the transcriptional complex ISGF3. Inhibiting RLR activation as well as neutralizing antibodies against IL-27 prevented TFH formation. DENV-induced CXCR5+PD-1+Bcl-6+ TFH cells secreted IL-21 and activated B cells to produce IgM and IgG. Notably, RLR activation by synthetic ligands also induced IL-27 secretion and TFH polarization. These results identify an innate mechanism by which antibodies develop during viral disease and identify RLR ligands as potent adjuvants for TFH-promoting vaccination strategies

AB - Follicular T helper cells (TFH) are fundamental in orchestrating effective antibody-mediated responses critical for immunity against viral infections and effective vaccines. However, it is unclear how virus infection leads to TFH induction. We here show that dengue virus (DENV) infection of human dendritic cells (DCs) drives TFH formation via crosstalk of RIG-I-like receptor (RLR) RIG-I and MDA5 with type I Interferon (IFN) signaling. DENV infection leads to RLR-dependent IKKε activation, which phosphorylates IFNα/β receptor-induced STAT1 to drive IL-27 production via the transcriptional complex ISGF3. Inhibiting RLR activation as well as neutralizing antibodies against IL-27 prevented TFH formation. DENV-induced CXCR5+PD-1+Bcl-6+ TFH cells secreted IL-21 and activated B cells to produce IgM and IgG. Notably, RLR activation by synthetic ligands also induced IL-27 secretion and TFH polarization. These results identify an innate mechanism by which antibodies develop during viral disease and identify RLR ligands as potent adjuvants for TFH-promoting vaccination strategies

U2 - 10.1371/journal.ppat.1006738

DO - 10.1371/journal.ppat.1006738

M3 - Article

C2 - 29186193

VL - 13

SP - e1006738

JO - PLoS pathogens

JF - PLoS pathogens

SN - 1553-7366

IS - 11

ER -

ID: 4419868