American Society of Hirudotherapy

A novel Toll like receptor with two TIR domains (HcToll-2) is involved in regulation of antimicrobial peptide gene expression of Hyriopsis cumingii.

Research article published in Developmental and comparative immunology (2014)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: In vitro / laboratoryAntimicrobial ResistanceDrug DevelopmentGenomics & ProteomicsRen Q et al. · Developmental and comparative immunology, 2014

Abstract

Animal Toll-like receptors (TLRs) are involved in innate immunity. Toll proteins are generally transmembrane proteins. In this study, an atypical Toll-like receptor (HcToll-2) was identified from the triangle-shell pearl mussel Hyriopsis cumingii, which belongs to phylum Mollusca. Unlike the typical Toll like receptors with extracellular leucine-rich repeats (LRRs), transmembrane, and intracellular Toll/interleukin-1 receptor (TIR) domains, HcToll-2 has two homologous TIR domains located at the C-terminal (designated as HcTIR1 and HcTIR2) and lacks a transmembrane domain. Phylogenetic analysis showed that HcTIR1 was clustered with TIR of sea anemone Toll, and HcTIR2 was clustered with TIR of Drosophila Toll. HcToll-2 mRNA could be detected in the hepatopancreas and was upregulated after challenge with Escherichia coli and Staphylococcus aureus. Recombinant HcLRR protein with GST tag could bind to bacteria and also to LPS and PGN. Over-expression of both HcTIR1 and HcTIR2 induced drosomycin genes in Drosophila S2 cells. RNAi analysis showed that HcToll-2 was required for the expression of theromacin, which is a cysteine-rich antimicrobial peptide (AMP) gene. This research is the first report of an atypical Toll-like receptor HcToll-2 involved in antibacterial immunity through induction of AMP expression.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, Non-U.S. Gov't
Indexed MeSH termsAmino Acid SequenceAnimalsAntimicrobial Cationic PeptidesBase SequenceCell LineConsensus SequenceDrosophila melanogasterGram-Negative BacteriaGram-Positive BacteriaLipopolysaccharidesMolecular Sequence DataPhylogeny

Summary

Animal Toll-like receptors (TLRs) are involved in innate immunity. Toll proteins are generally transmembrane proteins. In this study, an atypical Toll-like receptor (HcToll-2) was identified from the triangle-shell pearl mussel Hyriopsis cumingii, which belongs to phylum Mollusca.

Why This Matters for Hirudotherapy

Naming/scope note: despite sitting in an ASH research index, this study is not about leeches at all. It identifies and characterizes an atypical Toll-like receptor (HcToll-2) with two TIR domains and no transmembrane region in the freshwater triangle-shell pearl mussel Hyriopsis cumingii (phylum Mollusca), showing its mRNA rises after Escherichia coli and Staphylococcus aureus challenge and that it is required for expression of the antimicrobial peptide theromacin. The only thread to hirudotherapy is indirect: theromacin was originally described in a leech, and invertebrate innate-immunity/antimicrobial-peptide biology is part of why leech secretions are studied. Caveat: this is a preclinical/in-vitro molecular immunology study in a mussel, not a leech or any medicinal Hirudo species, and it makes no hirudotherapy claim; its relevance to the leech-therapy story is minimal and should not be overstated.

Citation

A novel Toll like receptor with two TIR domains (HcToll-2) is involved in regulation of antimicrobial peptide gene expression of Hyriopsis cumingii.

Ren Q et al. · Developmental and comparative immunology, 2014

Added to ASH library: May 28, 2026 · Site last updated: June 18, 2026

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