<p>Hard ticks depend upon an ability to precisely and dynamically regulate their saliva to successfully evade host haemostatic and immune defences during extended blood feeding. Although pilocarpine, an exogenous muscarinic acetylcholine receptor (mAChR) agonist, can stimulate salivation experimentally, the endogenous control of saliva secretion by acetylcholine remains poorly understood. Here, we identify and characterise two pharmacologically distinct mAChRs (type A and B) in the genome of the medically important tick <i>Ixodes ricinus</i>. Molecular dynamics simulations and targeted mutagenesis reveal that type B mAChRs exhibit an atypical muscarinic profile, suggesting unconventional receptor signalling. Combining immunolabelling, in vivo pharmacology, and proteomics, we show that specific central neurons interact with distinct salivary gland regions via mAChR type-specific axons, coordinating fluid and protein secretion through separate acini and likely acting upstream of a neuropeptide-dependent cascade. This previously unrecognised mechanism of neural control offers new insights into how ticks modulate their saliva advancing our understanding of vector-host interactions, with potential implications for disrupting pathogen transmission.</p>

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Two types of axonal muscarinic acetylcholine receptors mediate formation of saliva cocktail in the tick Ixodes ricinus

  • Cáinà Nìng,
  • James J. Valdés,
  • Lourdes Mateos-Hernández,
  • Sabine Rakotobe,
  • Lianet Abuin-Denis,
  • Nadia Haddad,
  • Lívia Šofranková,
  • Mirko Slovák,
  • Khalid Boussaine,
  • Alison Cartereau,
  • Emiliane Taillebois,
  • Houssam Attoui,
  • Helena Frantová,
  • Veronika Urbanová,
  • Tereza Kozelková,
  • Filip Dyčka,
  • Petr Kopáček,
  • Ondřej Hajdušek,
  • Radek Šíma,
  • Jiří Týč,
  • Tomáš Bílý,
  • Martina Tesařová,
  • Marie Vancová,
  • Jan Perner,
  • Steeve H. Thany,
  • Ladislav Šimo

摘要

Hard ticks depend upon an ability to precisely and dynamically regulate their saliva to successfully evade host haemostatic and immune defences during extended blood feeding. Although pilocarpine, an exogenous muscarinic acetylcholine receptor (mAChR) agonist, can stimulate salivation experimentally, the endogenous control of saliva secretion by acetylcholine remains poorly understood. Here, we identify and characterise two pharmacologically distinct mAChRs (type A and B) in the genome of the medically important tick Ixodes ricinus. Molecular dynamics simulations and targeted mutagenesis reveal that type B mAChRs exhibit an atypical muscarinic profile, suggesting unconventional receptor signalling. Combining immunolabelling, in vivo pharmacology, and proteomics, we show that specific central neurons interact with distinct salivary gland regions via mAChR type-specific axons, coordinating fluid and protein secretion through separate acini and likely acting upstream of a neuropeptide-dependent cascade. This previously unrecognised mechanism of neural control offers new insights into how ticks modulate their saliva advancing our understanding of vector-host interactions, with potential implications for disrupting pathogen transmission.