Molecular interactions between ticks (Ixodidae) and cattle: Salivary proteins, host immune modulation, and pathogen...

Ticks (Ixodidae) are major ectoparasites of cattle and highly effective vectors of pathogens responsible for babesiosis, theileriosis, and anaplasmosis. Their capacity to remain attached and blood feed for prolonged periods is underpinned by a finely regulated molecular dialogue at the tick cattle skin interface, driven primarily by the continuous injection of saliva throughout feeding. Tick saliva is a complex and dynamically regulated mixture of proteins, peptides, and small molecules that counter host hemostatic, inflammatory, and immune defenses, thereby ensuring uninterrupted blood uptake and creating a permissive microenvironment for pathogen establishment. Increasing evidence indicates that saliva is not merely a passive vehicle for pathogen delivery but actively promotes saliva-assisted transmission (SAT), whereby saliva-mediated immunomodulation enhances pathogen transmission efficiency and early infection success at the bite site. At the gene and pathway level, cattle responses to tick feeding involve extensive reprogramming of innate and adaptive immune networks in the skin, characterized by suppression or redirection of inflammatory signaling, antigen presentation, and effector mechanisms that would otherwise limit feeding and pathogen survival. Concurrently, the remarkable diversity of the tick sialome shaped by feeding stage specific expression and extensive functional redundancy provides multiple molecular routes to inhibit coagulation, neutralize inflammatory mediators, and modulate leukocyte recruitment, complicating efforts to link individual salivary molecules to discrete host outcomes. Together, these mechanistic insights provide a foundation for translational advances in veterinary medicine, including anti-tick vaccines that target conserved tick molecules to reduce infestation and potentially disrupt pathogen transmission. This review synthesizes current knowledge on (i) the molecular composition and functional classes of tick salivary factors relevant to cattle, (ii) cattle immune gene and pathway modulation at tick bite sites, and (iii) saliva-driven mechanisms that facilitate tick-borne pathogen transmission, while highlighting key knowledge gaps and priorities for next generation control strategies.