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

Abstract

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.

Sympatric versus allopatric evolutionary contexts shape differential immune response in Biomphalaria / Schistosoma interaction

“…miRNAs are known to regulate numerous biological processes, including key immune response genes [59, 60]. Recent work has demonstrated that circulating small non-coding RNAs from parasites have hijack roles against host metabolism, notably in the interaction of schistosomes with their vertebrate hosts [61–63]. Such non-coding RNAs could act as exogenous miRNAs to interfere with or circumvent the host immune system.…”

Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging

“…Given the small number of parasites committed to sexual differentiation, another obvious application of scRNA-seq is to define the differentiation hierarchy and underlying molecular mechanisms of sexual differentiation into male and female gametocytes to identify mating-type determination [14,15,27]. In addition, since RBCs also have RNA transcripts [49][50][51] with the potential for regulating malaria infection [52,53] and intercellular communication [54], it will be interesting to perform parallel transcriptome profiling of the host RBCs and infecting parasites to identify novel genetic determinants of invasion. Similar approaches can also be used to dissect host-pathogen interactions in hepatocyte and mosquito host cells.…”

Different Erythrocyte MicroRNA Profiles in Low- and High-Altitude Individuals

“…Therefore, more attention should be directed toward understanding RBC miRNAs. It has been reported that RBC miRNAs not only inhibit the reproduction of Plasmodium falciparum in patients with sickle cell anemia but are also associated with the development of bodily disorders (Lamonte et al, 2012 ; Duan et al, 2016 , 2017 ; Walzer and Chi, 2017 ; Wu et al, 2017 ). In this study, we hypothesized that high-altitude hypoxic environments likely impact RBC miRNA expression levels.…”