STRAP positively regulates TLR3-triggered signaling pathway.

Area of Science:

• Immunology
• Molecular Biology
• Cell Signaling

Background:

• Toll-like receptor (TLR) signaling is crucial for innate immunity, activating nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF).
• Previous research indicated STRAP's role in NF-κB activation and pro-inflammatory cytokine production via TAK1 and IKKα.
• The function of STRAP in TLR3-mediated signaling and type I interferon (IFN) production remained unclear.

Purpose of the Study:

• To elucidate the role of STRAP in Toll-like receptor 3 (TLR3) signaling pathways.
• To investigate STRAP's involvement in TRIF/TBK1-mediated activation and subsequent type I interferon production.
• To determine the functional domains of STRAP critical for TLR3-mediated immune responses.

Main Methods:

• Investigated STRAP interactions with key signaling molecules like TBK1 and IRF3.
• Utilized knockdown and overexpression of STRAP in TLR3 agonist-stimulated macrophages.
• Analyzed the impact of STRAP manipulation on pro-inflammatory cytokine and interferon production.
• Performed functional analysis of STRAP's C-terminus in TLR3-mediated signaling.

Main Results:

• STRAP functions as a scaffold protein in TLR3-triggered signaling, interacting with TBK1 and IRF3.
• STRAP enhances interferon-beta (IFN-β) production by facilitating TBK1-IRF3 interaction.
• STRAP knockdown decreased, while overexpression enhanced, pro-inflammatory cytokine and IFN levels in response to TLR3 stimulation.
• The C-terminus of STRAP is essential for its activity in TLR3-mediated IL-6 and IFN-β production.

Conclusions:

• STRAP is a positive regulator of TLR3-mediated signaling pathways.
• STRAP plays a significant role in both NF-κB and IRF activation downstream of TLR3.
• STRAP's scaffolding function is critical for robust innate immune responses, including cytokine and interferon production.