Deciphering Babesia-Vector Interactions

Abstract

Understanding host-pathogen-tick interactions remains a vitally important issue that might be better understood by basic research focused on each of the dyad interplays. Pathogens gain access to either the vector or host during tick feeding when ticks are confronted with strong hemostatic, inflammatory and immune responses. A prominent example of this is the Babesia spp.-tick-vertebrate host relationship. Babesia spp. are intraerythrocytic apicomplexan organisms spread worldwide, with a complex life cycle. The presence of transovarial transmission in almost all the Babesia species is the main difference between their life cycle and that of other piroplasmida. With more than 100 species described so far, Babesia are the second most commonly found blood parasite of mammals after trypanosomes. The prevalence of Babesia spp. infection is increasing worldwide and is currently classified as an emerging zoonosis. Babesia microti and Babesia divergens are the most frequent etiological agents associated with human babesiosis in North America and Europe, respectively. Although the Babesia-tick system has been extensively researched, the currently available prophylactic and control methods are not efficient, and chemotherapeutic treatment is limited. Studying the molecular changes induced by the presence of Babesia in the vector will not only elucidate the strategies used by the protozoa to overcome mechanical and immune barriers, but will also contribute toward the discovery of important tick molecules that have a role in vector capacity. This review provides an overview of the identified molecules involved in Babesia-tick interactions, with an emphasis on the fundamentally important ones for pathogen acquisition and transmission.

Keywords: Babesia spp.; babesiosis; tick-borne diseases; tick-pathogen interaction; vector.

Figure 1

Diagram representing tick molecules implicated in Babesia spp. acquisition and transmission by the vector. When ticks feed on Babesia-infected animals, parasites within red blood cellsreach and penetrate the tick midgut peritrophic membrane to invade the epithelial cells (in the figure center). Once these cells are infected, transcriptional factors, such as subolesin, can regulate protein expression in several cellular pathways, facilitating Babesia infection. In the microvilli of the midgut cells, parasite zygotes will probably interact with a tick glycoprotein (Bm86) and a tick receptor of the outer surface protein A (TROSPA). Inside the epithelial cells, mitochondria porins (VDAC) can bind to Babesia kinete proteins promoting plasminogen activation in the cell surface, allowing their passage to the haemolymph. Once here, the haemocytes can phagocyte circulating parasites and the tick antimicrobial molecules such as, longicin, micropulsin, longipain, LRR-domain and Kunitz-type protease inhibitors are activated potentially reducing the infection in the vector. If the infectious parasites surpass these barriers of defense, they will be capable to spread across the tissues and invade ovaries (represented in the bottom of the figure) and SGs (represented in the top of the figure). In the ovary, the interaction of Babesia molecules with tick vitellogenin and TROSPA receptors may contribute for the occurrence of transovarial transmission; while in the SGs, Babesia interacts with TROSPA and calreticulin.