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<33>RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production

最後更新日期 : 2018-05-18

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

Joris K. Sprokholt, Tanja M. Kaptein, John L. van Hamme, Ronald J. Overmars,
Sonja I. Gringhuis, Teunis B. H. Geijtenbeek

PLoS Pathog. 2017 Nov 29;13(11):e1006738.

 

Speaker: Po-Hsiang Huang (黃柏翔)                            Time: 15:10~16:00, May 23, 2018

Commentator: Dr. Pin Ling (凌斌老師)      　　　　Place: Room 601

 

Abstract:

Dengue virus (DENV) is a mosquito-borne pathogen, and there are 400 million infected people annually. Furthermore, we still have not developed the specific antivirals or effective vaccines against DENV. Therefore, the mechanism of antibody production should be understood comprehensively to improve drug or vaccine development. Antibody is the critical immune response for the host to control and clear virus infections. Dendritic cells (DCs) and follicular T helper cells (TFH) play important roles for the antibody production. Here author shows that DENV-infected human DCs induce CXCR5+PD-1+Bcl-6+ TFH formation via RIG-I-like receptor (RLR) and type I interferon (IFN). RLR sensing DENV RNA replication modulates IFNα/βR signaling and leads to IKKε activation that phosphorylates STAT1 to drive the transcriptional complex ISGF3 inducing IL-27 production. Both RLR activation and IL-27 are pivotal for the formation of TFH cells. DENV-induced CXCR5+PD-1+Bcl-6+ TFH cells activate B cells to produce IgM and IgG against dengue virus. Especially, synthetic ligands that directly trigger RLR also induce TFH polarization, IL-27 and antibody production. These results identify a virus detection mechanism that induces robust antibody production during DENV infection and its ligands as potential adjuvants in developing DENV vaccine.

 

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