HMN 2026: What a new saliva control map could mean for Lyme prevention

Ticks are major vectors of infectious diseases, affecting both animals and humans. Their ability to remain attached to a host and feed on their blood over the course of several days derives from their saliva, which prevents blood clotting and reduces the host’s immune defenses.

Previous work on tick saliva has primarily focused on identifying its involvement in suppressing the host defense system and facilitating pathogen transmission. One question remained: how does the tick control its salivation process?

To address this question, an international research team led by INRAE, in collaboration with ANSES, ENVA, and the University of Orléans, investigated how Ixodes ricinus—the primary tick species in Europe, responsible for transmitting Lyme disease and tick-borne encephalitis—regulates the activity of its salivary glands. The study is published in the journal Nature Communications.

How a dual signaling system powers tick feeding

Using computer models and microscopy techniques, the research team found that the tick’s nervous system can precisely regulate the activity of its salivary glands during blood feeding. This control is achieved through two distinct yet complementary signaling pathways involving receptors sensitive to the neurotransmitter acetylcholine. To explore the roles of these pathways, the researchers tested 37 substances—including pilocarpine and atropine (which are alkaloids)—identifying compounds that either activated or blocked one or both receptors.

The findings revealed that one pathway governs the continuous secretion of salivary fluid, while both pathways must work in tandem to produce the full salivary cocktail, including key proteins needed for blood feeding. This dual control enables the tick to finely tune the quantity and composition of its saliva while attached to a host.

A key contribution of this study is providing evidence that acetylcholine, a compound naturally present in ticks, is a powerful natural stimulator of salivation in female ticks. Moreover, the team discovered that one of the identified receptors is specific to invertebrates and absent in mammals, including humans, suggesting the potential for developing targeted strategies to disrupt tick feeding without harming the host.

Better understanding the enemy to develop effective countermeasures

Inhibiting salivation is a crucial step in preventing both blood feeding and pathogen transmission. Targeting the tick’s nervous system and its connection to the salivary glands presents a particularly promising strategy for future control efforts. This foundational research rests on a simple principle: understanding the enemy enables more effective and targeted control measures. A deeper understanding of these mechanisms—which are likely shared across different tick species worldwide—could lead to more universal and sustainable control strategies.

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