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The functional effects of physical interactions among Toll-like receptors 7, 8, and 9

Jianyong Wang1, Yu Shao, Teri A Bennett

  • 1Department of Pharmacology, 3M Pharmaceutical Division, St. Paul, Minnesota 55144, USA.

The Journal of Biological Chemistry
|October 17, 2006
PubMed

Insights

Toll-like receptors 8 (TLR8) and 9 (TLR9) inhibit the function of TLR7, revealing novel inhibitory interactions among endosomal TLRs. These findings suggest a role for TLR interactions in modulating host-pathogen recognition and inflammatory responses.

Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Toll-like receptors (TLRs) are crucial for innate immunity, recognizing pathogen-associated molecular patterns (PAMPs).
  • While plasma membrane-localized TLRs (TLR1, TLR2, TLR4, TLR6) exhibit cooperative interactions, such functional crosstalk among endosomal TLRs (TLR7, TLR8, TLR9) remains largely unexplored.
  • Endosomal TLRs recognize oligonucleotide-based PAMPs and their cooperative signaling in response to agonists is not well understood.

Purpose of the Study:

  • To investigate the functional interactions between endosomal Toll-like receptors TLR7, TLR8, and TLR9.
  • To determine if TLRs 7, 8, and 9 modulate each other's signaling pathways in response to specific agonists.

Main Methods:

  • Utilized HEK293 cells co-transfected with pairs of TLR7, TLR8, and TLR9.
  • Employed small molecule TLR agonists to selectively activate individual TLRs.
  • Assessed functional outcomes by observing inflammatory signaling modulation.

Main Results:

  • TLR8 was found to inhibit both TLR7 and TLR9 signaling.
  • TLR9 was shown to inhibit TLR7 signaling, but not vice versa.
  • These inhibitory effects were confirmed to involve direct or indirect physical interactions between the TLRs.
  • Murine TLR8 demonstrated inhibitory effects on both murine and human TLR7.

Conclusions:

  • This study provides the first evidence of functional inhibition among endosomal TLRs (TLR7, TLR8, TLR9).
  • The observed inhibitory interactions, mediated by physical contact, suggest a mechanism for fine-tuning inflammatory responses.
  • These findings highlight the complexity of TLR-mediated immunity and its potential role in balancing host-pathogen recognition and inflammatory outcomes.

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