American Society of Hirudotherapy

Antimicrobial Role of RNASET2 Protein During Innate Immune Response in the Medicinal Leech

Research article published in Frontiers in immunology (2020)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Preclinical (animal)Genomics & ProteomicsSafety & Infection ControlAntimicrobial ResistanceBaranzini N et al. · Frontiers in immunology, 2020

Abstract

The innate immune response represents a first-line defense against pathogen infection that has been widely conserved throughout evolution. Using the invertebrate Hirudo verbana (Annelida, Hirudinea) as an experimental model, we show here that the RNASET2 ribonuclease is directly involved in the immune response against Gram-positive bacteria. Injection of lipoteichoic acid (LTA), a key component of Gram-positive bacteria cell wall, into the leech body wall induced a massive migration of granulocytes and macrophages expressing TLR2 (the key receptor involved in the response to Gram-positive bacteria) toward the challenged/inoculated area. We hypothesized that the endogenous leech RNASET2 protein (HvRNASET2) might be involved in the antimicrobial response, as already described for other vertebrate ribonucleases, such as RNase3 and RNase7. In support of our hypothesis, HvRNASET2 was mainly localized in the granules of granulocytes, and its release in the extracellular matrix triggered the recruitment of macrophages toward the area stimulated with LTA. The activity of HvRNASET2 was also evaluated on Staphylococcus aureus living cells by means of light, transmission, and scanning electron microscopy analysis. HvRNASET2 injection triggered the formation of S. aureus clumps following a direct interaction with the bacterial cell wall, as demonstrated by immunogold assay. Taken together, our data support the notion that, during the early phase of leech immune response, granulocyte-released HvRNASET2 triggers bacterial clumps formation and, at the same time, actively recruits phagocytic macrophages in order to elicit a rapid and effective eradication of the infecting microorganisms from inoculated area.

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 termsAnimalsCD11b AntigenHirudo medicinalisImmunity, InnateLipopolysaccharidesMacrophagesPhagocytosisRibonucleasesTeichoic AcidsToll-Like Receptor 2

Summary

The innate immune response represents a first-line defense against pathogen infection that has been widely conserved throughout evolution.

Why This Matters for Hirudotherapy

This study examined the role of the endogenous ribonuclease HvRNASET2 in the medicinal leech Hirudo verbana's innate immune response to Gram-positive bacteria, showing that the protein is stored in granulocyte granules, is released upon lipoteichoic acid challenge, recruits macrophages, and induces clumping of Staphylococcus aureus through direct cell-wall interaction. For hirudotherapy and ASH's domain, this work is directly relevant because it characterizes an intrinsic antimicrobial defense mechanism in the very species used clinically, informing our understanding of how medicinal leeches naturally resist bacterial colonization—an important consideration given infection risk associated with leech therapy. The findings may also stimulate interest in whether leech-derived RNASET2 or related salivary components possess exploitable antimicrobial properties. However, the study is experimental and restricted to the leech's own immune biology; it does not evaluate therapeutic efficacy in mammalian or clinical contexts, nor does it demonstrate that HvRNASET2 is secreted into saliva at functionally relevant concentrations during feeding or therapy.

Citation

Antimicrobial Role of RNASET2 Protein During Innate Immune Response in the Medicinal Leech

Baranzini N et al. · Frontiers in immunology, 2020

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

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