Trans-kingdom small RNA transfer during host-pathogen interactions: The case of P. falciparum and erythrocytes

This review focuses on the role of trans-kingdom movement of small RNA (sRNA) molecules between parasites, particularly Plasmodium falciparum, and their respective host cells. While the intercellular transfer of sRNAs within organisms is well recognized, recent studies illustrate many examples of trans-kingdom sRNA exchange within the context of host-parasite interactions. These interactions are predominantly found in the transfer of host sRNAs between erythrocytes and the invading P. falciparum, as well as other host cell types. In addition, parasite-encoded sRNAs can also be transferred to host cells to evade the immune system. The transport of these parasite sRNAs in the body fluids of the host may also offer means to detect and monitor the parasite infection. These isolated examples may only represent the tip of the iceberg in which the transfer of sRNA between host and parasites is a critical aspect of host-pathogen interactions. In addition, the levels of these sRNAs and their speed of transfer may vary dramatically under different contexts to push the biologic equilibrium toward the benefit of hosts vs. parasites. Therefore, these sRNA transfers may offer potential strategies to detect, prevent or treat parasite infections. Here, we review a brief history of the discovery of host erythrocyte sRNAs, their transfers and interactions in the context of P. falciparum infection. We also provide examples and discuss the functional significance of the reciprocal transfer of parasite-encoded sRNAs into hosts. These understandings of sRNA exchanges are put in the context of their implications for parasite pathogenesis, host defenses and the evolution of host polymorphisms driven by host interactions with these parasites.