Abstract
Exosomes are small extracellular vesicles that carry proteins, lipids, and nucleic acids. They are circulated in many body fluids and play an important role in intercellular communications. MicroRNAs (miRNAs), as major components of exosomes, are often regulated in many diseases including bacterial and viral infections. Functionally, exosome-carried miRNAs interact with various immune cells and affect their behavior. Little is known whether exosomal miRNAs are regulated during scrub typhus, a potentially lethal infection caused by intracellular bacteria, Orientia tsutsugamushi. In the present study, we utilized a scrub typhus mouse model and collected serum at various time points post infection. A custom quantitative PCR array covering 92 murine miRNAs was used to profile serum exosomal miRNAs. A total of 12 miRNAs were found to be significantly up- or down-regulated at least at one time point post infection when compared to uninfected animals. Further analysis identified multiple miRNAs in the let-7 family that were consistently down-regulated at early and late phase of infection. Functionally, serum exosomes isolated from infected mice displayed strong proinflammatory effect when incubated with bone marrow-derived macrophages. Our data revealed dynamic regulations of serum exosomal miRNA during scrub typhus infection, which could significantly influence host immune responses and disease outcome.
Highlights
Scrub typhus is an acute febrile infectious disease caused by intracellular bacteria of Orientia tsutsugamushi that is transmitted by larval feeding of chigger mites (Trombiculidae), mostly Leptotrombidium spp
Characterization of Serum Exosomes Isolated from Orientia Tsutsugamushi-Infected Mice
To study serum exosomes during O. tsutsugamushi infection, a lethal murine model of scrub typhus was used as previously conducted in our laboratory [12]
Summary
Scrub typhus is an acute febrile infectious disease caused by intracellular bacteria of Orientia tsutsugamushi that is transmitted by larval feeding of chigger mites (Trombiculidae), mostly Leptotrombidium spp. O. tsutsugamushi is able to evade destruction by macrophages [5] and subvert dendritic cell functions [6], possibly leading to delayed and constrained adaptive immune responses that are essential for host immune protection against scrub typhus [7]. Exosomes are small extracellular vesicles (usually 40–150 nm) secreted by virtually all cell types. They play important roles in intercellular communication through proteins, Microorganisms 2021, 9, 80. Exosomes derived from antigen presenting cells (APCs), such as dendritic cells (DCs), can interact with the adaptive immune system and stimulate both T cell and B cell responses [10]. We used a scrub typhus mouse model and investigated miRNA regulations and immunomodulatory functions of serum exosomes isolated from O. tsutsugamushi-infected mice
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