Human macrophages release exosomes containing anti-inflammatory microRNAs after phagocytosis of Leishmania infantum

Cinthia Hudachek; Bayan Zhanbolat; Yani Chen; Mary Wilson

doi:10.3389/fimmu.2025.1593829

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Human macrophages release exosomes containing anti-inflammatory microRNAs after phagocytosis of Leishmania infantum

Journal article

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Human macrophages release exosomes containing anti-inflammatory microRNAs after phagocytosis of Leishmania infantum

Cinthia Hudachek, Bayan Zhanbolat, Yani Chen and Mary Wilson

Frontiers in immunology, Vol.16, 1593829

12/01/2025

DOI: 10.3389/fimmu.2025.1593829

PMCID: PMC12727609

PMID: 41451223

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Abstract

Introduction: The protozoan Leishmania infantum causes visceral leishmaniasis, a disease associated with suppressed systemic innate and adaptive immune responses. Mechanisms underlying the generalized immune suppression are incompletely understood. Exosomes are a subset of microvesicles released from eukaryotic cells, which contain proteins, lipids, and nucleic acids, including microRNAs (miRNAs). These small regulatory RNAs can simultaneously modify the expression of many genes and pathways. We hypothesized that L. infantum infection of macrophages induces the release of exosomes containing immunomodulatory miRNAs that contribute to systemic immunosuppression during visceral leishmaniasis. Methods: Using NanoString arrays, we profiled exosomal miRNAs released by infected versus uninfected human macrophages. Differential expression was validated by RT-qPCR, and functional effects were tested by transfecting miR-mimics. Results: Several miRNAs were augmented in infected exosomes, including hsa-miR-223-3p which has anti-inflammatory activities. Previous studies showed that the NLRP3 inflammasome pathway might be targeted by differentially expressed miRNAs, a hypothesis that was confirmed in transfected THP-1 monocytic cells overexpressing hsa-miR-223-3p. Discussion: We show that L. infantum infection induces the release of exosomes containing miRNAs that are capable of modifying the host immune environment, possibly suppressing microbicidal pathways and favoring parasite survival.

Immunosuppression

Inflammation

Blood & organ donations

Exosomes

Immune response

Immunomodulation

Inflammasomes

Leishmania infantum

Lipids

Macrophages

Microbicides

MicroRNAs

miRNA

Monocytes

Parasites

Parasitic diseases

Phagocytosis

Visceral leishmaniasis

Details

Title: Subtitle: Human macrophages release exosomes containing anti-inflammatory microRNAs after phagocytosis of Leishmania infantum
Creators: Cinthia Hudachek - University of Iowa
Bayan Zhanbolat - University of Iowa
Yani Chen - University of Iowa
Mary Wilson - University of Iowa
Resource Type: Journal article
Publication Details: Frontiers in immunology, Vol.16, 1593829
DOI: 10.3389/fimmu.2025.1593829
PMID: 41451223
PMCID: PMC12727609
NLM abbreviation: Front Immunol
ISSN: 1664-3224
eISSN: 1664-3224
Publisher: Frontiers Media SA
Grant note: National Institute of Allergy and Infectious DiseasesU.S. Department of Veterans Affairs: I01 BX001983
The author(s) declared that financial support was received for this work and/or its publication. The work was supported by Merit Review grants I01 BX001983 and I01 BX000536 from the US Department of Veterans' Affairs (MW). The work was performed while CH was supported by NIH T32 AI007511.
Language: English
Date published: 12/01/2025
Academic Unit: Microbiology and Immunology; Infectious Diseases; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9985091804502771

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