The Flagellin: Allergen Fusion Protein rFlaA:Betv1 Activates Macrophages
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  • Release Date: 2021-12-22
  • flagellin
  • TLR5
  • allergen
  • Bet v 1
  • fusion protein
  • metabolism
Video Introduction

This video is adapted from 10.3390/cells10102614

TLR5 ligand flagellin-containing fusion proteins are potential vaccine candidates for many diseases. A recombinant fusion protein of flagellin A and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) modulates immune responses in vitro and in vivo. Authors studied the effects of rFlaA:Betv1 on bone marrow-derived macrophages (BMDMs). BMDMs differentiated from BALB/c, C57BL/6, TLR5−/−, or MyD88−/− mice were pre-treated with inhibitors, stimulated with rFlaA:Betv1 or respective controls, and analyzed for activation, cytokine secretion, metabolic state, RNA transcriptome, and modulation of allergen-specific Th2 responses. Stimulation of BMDMs with rFlaA:Betv1 resulted in MyD88-dependent production of IL-1β, IL-6, TNF-α, IL-10, CD69 upregulation, and a pronounced shift towards glycolysis paralleled by activation of MAPK, NFκB, and mTOR signaling. Inhibition of either mTOR (rapamycin) or SAP/JNK-MAPK signaling (SP600125) resulted in dose-dependent metabolic suppression. In BMDM and T cell co-cultures, rFlaA:Betv1 stimulation suppressed rBet v 1-induced IL-5 and IL-13 secretion while inducing IFN-γ production. mRNA-Seq analyses showed HIF-1a, JAK, STAT, phagosome, NLR, NFκB, TNF, TLR, and chemokine signaling to participate in the interplay of cell activation, glycolysis, and immune response. rFlaA:Betv1 strongly activated BMDMs, resulting in MyD88−, MAPK−, and mTOR-dependent enhancement of glucose metabolism. The results suggest macrophages are important target cells to consider during restauration of allergen tolerance during AIT.

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Schülke, S. The Flagellin: Allergen Fusion Protein rFlaA:Betv1 Activates Macrophages. Encyclopedia. Available online: https://encyclopedia.pub/video/video_detail/151 (accessed on 13 April 2024).
Schülke S. The Flagellin: Allergen Fusion Protein rFlaA:Betv1 Activates Macrophages. Encyclopedia. Available at: https://encyclopedia.pub/video/video_detail/151. Accessed April 13, 2024.
Schülke, Stefan. "The Flagellin: Allergen Fusion Protein rFlaA:Betv1 Activates Macrophages" Encyclopedia, https://encyclopedia.pub/video/video_detail/151 (accessed April 13, 2024).
Schülke, S. (2021, December 22). The Flagellin: Allergen Fusion Protein rFlaA:Betv1 Activates Macrophages. In Encyclopedia. https://encyclopedia.pub/video/video_detail/151
Schülke, Stefan. "The Flagellin: Allergen Fusion Protein rFlaA:Betv1 Activates Macrophages." Encyclopedia. Web. 22 December, 2021.