Regulation of Serum Exosomal MicroRNAs in Mice Infected with Orientia tsutsugamushi
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Isolation and Characterization of Extracellular Vesicles from Adult Schistosoma japonicum
Published on: May 22, 2018
Le Jiang1, Tatyana Belinskaya1, Zhiwen Zhang1
1Viral and Rickettsial Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, MD 20910, USA.
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, Orientiatsutsugamushi. 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.
Insights
Scrub typhus infection alters serum exosomal microRNAs (miRNAs), impacting immune cell communication. These changes, particularly in the let-7 family, may influence host responses and disease severity.
Area of Science:
- Immunology
- Molecular Biology
- Microbiology
Background:
- Exosomes are key mediators of intercellular communication, carrying microRNAs (miRNAs) that influence immune responses.
- Scrub typhus, caused by *Orientia tsutsugamushi*, is a severe bacterial infection where the role of exosomal miRNAs remains unclear.
- Dysregulated miRNAs are implicated in various infectious diseases, affecting host immunity.
Purpose of the Study:
- To investigate the dynamic changes in serum exosomal miRNAs during scrub typhus infection.
- To understand the functional impact of these altered miRNAs on host immune cells.
Main Methods:
- A mouse model of scrub typhus was established, with serum collected at multiple time points post-infection.
- A custom quantitative PCR array was used to profile 92 miRNAs in serum exosomes.
- Exosomes from infected mice were incubated with bone marrow-derived macrophages to assess their immune effects.
Main Results:
- Twelve miRNAs showed significant differential regulation (up- or down-regulated) in serum exosomes during infection compared to controls.
- Several miRNAs from the let-7 family were consistently downregulated in both early and late stages of infection.
- Serum exosomes from infected mice induced a proinflammatory response in macrophages.
Conclusions:
- Scrub typhus infection dynamically alters the profile of serum exosomal miRNAs.
- Downregulation of specific miRNAs, like those in the let-7 family, may contribute to altered host immune responses.
- These findings highlight the potential role of exosomal miRNAs as biomarkers and therapeutic targets in scrub typhus.
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