Activation of the tick Toll pathway to control infection of Ixodes ricinus by the apicomplexan parasite Babesia microti.

Autor: Jalovecka, Marie, Malandrin, Laurence, Urbanova, Veronika, Mahmood, Sazzad, Snebergerova, Pavla, Peklanska, Miriama, Pavlasova, Veronika, Sima, Radek, Kopacek, Petr, Perner, Jan, Hajdusek, Ondrej
Zdroj: PLoS Pathogens; 12/16/2024, Vol. 20 Issue 12, p1-19, 19p
Abstrakt: The vector competence of blood-feeding arthropods is influenced by the interaction between pathogens and the immune system of the vector. The Toll and IMD (immune deficiency) signaling pathways play a key role in the regulation of innate immunity in both the Drosophila model and blood-feeding insects. However, in ticks (chelicerates), immune determination for pathogen acquisition and transmission has not yet been fully explored. Here, we have mapped homologs of insect Toll and IMD pathways in the European tick Ixodes ricinus, an important vector of human and animal diseases. We show that most genes of the Toll pathway are well conserved, whereas the IMD pathway has been greatly reduced. We therefore investigated the functions of the individual components of the tick Toll pathway and found that, unlike in Drosophila, it was specifically activated by Gram-negative bacteria. The activation of pathway induced the expression of defensin (defIR), the first identified downstream effector gene of the tick Toll pathway. Borrelia, an atypical bacterium and causative agent of Lyme borreliosis, bypassed Toll-mediated recognition in I. ricinus and also resisted systemic effector molecules when the Toll pathway was activated by silencing its repressor cactus via RNA interference. Babesia, an apicomplexan parasite, also avoided Toll-mediated recognition. Strikingly, unlike Borrelia, the number of Babesia parasites reaching the salivary glands during tick infection was significantly reduced by knocking down cactus. The simultaneous silencing of cactus and dorsal resulted in greater infections and underscored the importance of tick immunity in regulating parasite infections in these important disease vectors. Author summary: Ticks are important parasites of humans and animals worldwide. They act as vectors of numerous serious diseases such as Lyme disease, tick-borne encephalitis, rickettsiosis, babesiosis, and theileriosis. The innate immune system of ticks plays a crucial role in determining their vector competence and thus regulates the spread of pathogens. Through a series of RNA interference experiments in the European tick Ixodes ricinus, we were able to demonstrate the functionality of the tick Toll pathway and uncover its crucial role in both embryonic development and immunity. By identifying the read-out gene of the tick Toll pathway, defensin, we were able to show that the pathway can be stimulated by Escherichia coli and plays a key role in the balancing of Babesia infections. Our results provide insights into the functioning and evolutionary constraints of immune signaling pathways and contribute to the development of new defense mechanisms against arthropod-borne infections. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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