Micro RNA profiles of host extracellular vesicles are modulated by Ascaris suum infection but parasite extracellular vesicle miRNAs are systemically undetectable using in-depth miRNA sequencing

• Published in: International journal for parasitology Vol. 54; no. 13; pp. 691 - 696
• Main Authors: Whitehead, Bradley, Sørensen Rossen, Litten, Zippor, Mads, Boysen, Anders T., Indira Chandran, Vineesh, Skallerup, Per, Thamsborg, Stig M., Nejsum, Peter
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2024
• Subjects: Ascaris; Extracellular vesicles; Host-parasite communication; miRNA; Extracellular vesicles; miRNA; Host-parasite communication; Ascaris
• ISSN: 0020-7519; 1879-0135; 1879-0135
• DOI: 10.1016/j.ijpara.2024.08.001

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•Ascaris suum extracellular vesicles (EVs) are recognised by the host adaptive immune response.•Ascaris suum EVs generate antibody responses.•Ascaris suum EVs are not detectable in host plasma even under conditions mirroring natural infection with constant exposure.•Ascaris suum infection modulates host-EV micro RNA (miRNA) profiles.•There was increased detection of miRNAs associated with T reg, regulatory dendritic and B cells in infected pig EVs.
The intestinal helminth Ascaris lumbricoides infects over 800 million people. Infections are often chronic and immunity is not sterilizing due to host-immune modulation, therefore reinfection is common after antihelmintic treatment. We have previously demonstrated a role for Ascaris spp. extracellular vesicles (EVs) in host immune modulation but whether EVs are recognized by the adaptive immune system and are present systemically in the host remains unknown. Therefore, we employed a well-established trickle infection model in pigs to mimic natural Ascaris infection in humans. EVs were isolated from adult Ascaris suum followed by immunoblotting of EV and EV-depleted secretory fractions using plasma from infected and uninfected pigs. Next, EVs were isolated from pig plasma at day 56 post first infection and subjected to deep small RNAseq analysis. RNAs were aligned to A. suum and Sus scrofa miRNA complements to detect A. suum EVs and elucidate the host EV micro RNA (miRNA) response to infection, respectively. Infection generates robust antibody responses against A. suum EVs that is distinct from EV-depleted fractions. However, A. suum miRNAs were not detectable in EVs from the peripheral blood. Notably, host plasma-derived EV miRNA profiles showed significant changes between infected and uninfected pigs, indicating that Ascaris infection drives systemic changes in host EV composition.