Tick iron and heme metabolism - New target for an anti-tick intervention.

Ticks are blood-feeding parasites and vectors of serious human and animal diseases. Ixodes ricinus is a common tick in Europe, transmitting tick-borne encephalitis, Lyme borreliosis, anaplasmosis, or babesiosis. Immunization of hosts with recombinant tick proteins has, in theory, the potential to interfere with tick feeding and block transmission of pathogens from the tick to the host. However, the efficacy of tick antigens has, to date, not been fully sufficient to achieve this. We have focused on 11 in silico identified genes encoding proteins potentially involved in tick iron and heme metabolism. Quantitative real-time PCR (qRT-PCR) expression profiling was carried out to preferentially target proteins that are up-regulated during the blood meal. RNA interference (RNAi) was then used to score the relative importance of these genes in tick physiology. Finally, we performed vaccination screens to test the suitability of these proteins as vaccine candidates. These newly identified tick antigens have the potential to improve the available anti-tick vaccines.

Functional genomics of tick thioester-containing proteins reveal the ancient origin of the complement system.

Ticks are important ectoparasites and vectors of multiple human and animal diseases. The obligatory hemophagy of ticks provides a formidable route for parasite transmission from one host to another. Parasite survival inside the tick relies on the ability of a pathogen to escape or inhibit tick immune defenses, but the molecular interactions between the tick and its pathogens remain poorly understood. Here we report that tick genomes are unique in that they contain all known classes of the α(2)-macroglobulin family (α(2)M-F) proteins: α(2)-macroglobulin pan-protease inhibitors, C3 complement components, and insect thioester-containing and macroglobulin-related proteins. By using RNA interference-mediated gene silencing in the hard tick Ixodes ricinus we demonstrated the central role of a C3-like molecule in the phagocytosis of bacteria and revealed nonredundant functions for α(2)M-F proteins. Assessment of α(2)M-F functions in a single organism should significantly contribute to the general knowledge on the evolution and function of the complement system. Importantly, understanding the tick immune mechanisms should provide new concepts for efficient transmission blocking of tick-borne diseases.

Characterization of ferritin 2 for the control of tick infestations.

Ixodes ricinus is one the most abundant tick species in Europe and these ticks transmit pathogens causing human and animal diseases. The cattle ticks, Rhipicephalus (Boophilus) spp., affect cattle production in tropical and subtropical regions of the world. Development of vaccines directed against tick proteins may reduce tick infestations and the transmission of tick-borne pathogens. However, a limiting step in tick vaccine development has been the identification of tick protective antigens. Herein, the tick iron metabolism pathway was targeted in an effort to identify new tick protective antigens. Recombinant I. ricinus (IrFER2) and Rhipicephalus microplus (RmFER2) ferritin 2 proteins were expressed in Escherichia coli and used to immunize rabbits and cattle, respectively. Vaccination with IrFER2 reduced I. ricinus tick numbers, weight and fertility in rabbits with an overall vaccine efficacy (E) of 98%. Control of cattle tick, R. microplus and Rhipicephalus annulatus infestations was obtained in vaccinated cattle with overall E of 64% and 72%, respectively. Notably, the efficacy of the RmFER2 vaccine was similar to that obtained with Bm86 against R. microplus. These collective results demonstrated the feasibility of using ferritin 2 to develop vaccines for the control of tick infestations.