Acute Babesia microti Infection Is Associated With Marked Changes In The Expression Of Peripheral Blood Coding And Noncoding RNA 2301453

Abstract Introduction Babesiosis, an emerging tick-borne disease in the US caused by Babesia microti (Bm), has limited data on protective immune responses and host-parasite interactions. Peripheral blood transcriptomes have not previously been used to study the host immune response during babesiosis. Therefore, we studied peripheral blood transcriptomes in a timed infection mouse model to identify correlates of early, acute, and resolution stages of infection. Methods Female BALB/cJ mice were infected intraperitoneally with Bm and monitored for parasitemia by Giemsa-stained blood smears. Mice and controls were euthanized at days 5, 6, 7, 9, and 12 post-infection, and blood was collected for RNA isolation. RNA sequencing was performed using Illumina’s Stranded Total RNA Prep with Ribo-Zero Plus Kit and on a NextSeq2000. EdgeR assessed differentially expressed genes (DEGs), and QIAGEN Ingenuity Pathway Analysis was used for pathway analyses. Results Parasitemia increased through day 7, peaked at day 8, declined by day 9, and partially resurged on day 12 prior to resolution of parasitemia. The number of DEGs increased during infection. The host transcriptome on day 5 showed early innate immune activation, such as type I and II interferon pathways. Day 7 marked a major transition with more crisis parasite forms and robust activation of immune, metabolic, and proliferative pathways. On day 12 during resurgence, many of these pathways were further activated, including clotting cascade pathways. Conclusion This study characterizes temporal peripheral blood transcriptome changes during babesiosis. Early immune activation suggests rising parasitemia is not due to failed immune activation. Parasite clearance on day 7 aligns with activation of immune and non-traditional immune pathways. Upregulation of coagulation and other pathways during early resolution may contribute to clinical complications. These findings will guide therapeutic development and inform human transcriptome studies to identify correlates of disease severity. Funding Source Department of Defense W81XWH-20-1-0508 to D. Mordue Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)