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Peer-reviewedCC BYInternational journal of molecular sciences

microRNA and Regulatory Networks of Human Macrophage During Leishmania major In Vitro Infection

  • Sara Habouria1,2
  • Aymen Bali1,2
  • Aurora Diotallevi3
  • Ali Ben-Cheikh2
  • Chiraz Atri2
  • Mauro De Santi3
  • Sara Maestrini3
  • Luca Galluzzi3
  • Dhafer Laouini2
  • Fatma Zahra Guerfali2
  1. 1Faculty of Sciences of Tunis, University Tunis El Manar, Tunis 2092, Tunisia
  2. 2Laboratory of Transmission, Control and Immunobiology of Infections (LR16IPT02), Institut Pasteur de Tunis, Université de Tunis El Manar, Tunis 1002, Tunisia
  3. 3Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61032 Fano, Italy
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Abstract

Leishmania (L.) major modulates host microRNA (miR) expression to promote intracellular survival, yet the roles of specific miRs during early infection of human macrophages remain poorly defined. We investigated the dynamic regulation of miR-21-5p and miR-146a-5p in THP-1-derived macrophages infected with L. major over an early post-infection time course (3–48 h), alongside miR-30a-3p and miR-101-3p. Both miR-21-5p and miR-146a-5p were significantly upregulated during the early stages of infection (3–24 h) before declining by 48 h. Using antisense LNA inhibitors, we achieved independent single and dual silencing of both miRs, allowing us to dissect their functional contribution to host gene expression. In silico network analysis identified 887 shared and specific target genes, including NFKB1, MYC, STAT3, HIF1A, TNF, CXCL8, IL18, and XBP1. Silencing of miR-21-5p and miR-146a-5p at early time points relieved inhibitory control over several of these targets, notably increasing NF-κB, MYC, IL18 and XBP1 expression, and reducing TNF and sXBP1, consistent with their role as negative regulators of innate immune signaling. These findings identify miR-21-5p and miR-146a-5p as early, dynamic regulators of the human macrophage transcriptional response to L. major infection and identify their target genes as candidate biomarkers and therapeutic targets in cutaneous leishmaniasis.

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Cite

BibTeXRIS
BibTeX
@article{habouria2026microrna,
  title = {{microRNA and Regulatory Networks of Human Macrophage During Leishmania major In Vitro Infection}},
  author = {Sara Habouria and Aymen Bali and Aurora Diotallevi and Ali Ben-Cheikh and Chiraz Atri and Mauro De Santi and Sara Maestrini and Luca Galluzzi and Dhafer Laouini and Fatma Zahra Guerfali},
  journal = {International journal of molecular sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27198893},
  url = {https://europepmc.org/article/PMC/PMC13666224},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - microRNA and Regulatory Networks of Human Macrophage During Leishmania major In Vitro Infection
AU  - Sara Habouria
AU  - Aymen Bali
AU  - Aurora Diotallevi
AU  - Ali Ben-Cheikh
AU  - Chiraz Atri
AU  - Mauro De Santi
AU  - Sara Maestrini
AU  - Luca Galluzzi
AU  - Dhafer Laouini
AU  - Fatma Zahra Guerfali
PY  - 2026
DA  - 2026/10/01
JO  - International journal of molecular sciences
DO  - 10.3390/ijms27198893
UR  - https://europepmc.org/article/PMC/PMC13666224
AB  - Leishmania (L.) major modulates host microRNA (miR) expression to promote intracellular survival, yet the roles of specific miRs during early infection of human macrophages remain poorly defined. We investigated the dynamic regulation of miR-21-5p and miR-146a-5p in THP-1-derived macrophages infected with L. major over an early post-infection time course (3–48 h), alongside miR-30a-3p and miR-101-3p. Both miR-21-5p and miR-146a-5p were significantly upregulated during the early stages of infection (3–24 h) before declining by 48 h. Using antisense LNA inhibitors, we achieved independent single and dual silencing of both miRs, allowing us to dissect their functional contribution to host gene expression. In silico network analysis identified 887 shared and specific target genes, including NFKB1, MYC, STAT3, HIF1A, TNF, CXCL8, IL18, and XBP1. Silencing of miR-21-5p and miR-146a-5p at early time points relieved inhibitory control over several of these targets, notably increasing NF-κB, MYC, IL18 and XBP1 expression, and reducing TNF and sXBP1, consistent with their role as negative regulators of innate immune signaling. These findings identify miR-21-5p and miR-146a-5p as early, dynamic regulators of the human macrophage transcriptional response to L. major infection and identify their target genes as candidate biomarkers and therapeutic targets in cutaneous leishmaniasis.
SN  - 1422-0067
ER  -