Cited by 84Tuberculosis Research and EpidemiologyMicroRNA in disease regulationImmune Response and Inflammation

Actin-binding protein regulation by microRNAs as a novel microbial strategy to modulate phagocytosis by host cells: the case of N-Wasp and miR-142-3p

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Bettencourt, Paulo, Marion, Sabrina, Pires, David, Santos, Leonor F., Lastrucci, Claire, Carmo, Nuno, Blake, Jonathon, Benes, Vladimir +4 more·2013·Frontiers in Cellular and Infection Microbiology

Abstract

Mycobacterium tuberculosis (Mtb) is a successful intracellular pathogen that thrives in macrophages (Mφs). There is a need to better understand how Mtb alters cellular processes like phagolysosome biogenesis, a classical determinant of its pathogenesis. A central feature of this bacteria's strategy is the manipulation of Mφ actin. Here, we examined the role of microRNAs (miRNAs) as a potential mechanism in the regulation of actin-mediated events leading to phagocytosis in the context of mycobacteria infection. Given that non-virulent Mycobacterium smegmatis also controls actin filament assembly to prolong its intracellular survival inside host cells, we performed a global transcriptomic analysis to assess the modulation of miRNAs upon M. smegmatis infection of the murine Mφ cell line, J774A.1. This approach identified miR-142-3p as a key candidate to be involved in the regulation of actin dynamics required in phagocytosis. We unequivocally demonstrate that miR-142-3p targets N-Wasp, an actin-binding protein required during microbial challenge. A gain-of-function approach for miR-142-3p revealed a down-regulation of N-Wasp expression accompanied by a decrease of mycobacteria intake, while a loss-of-function approach yielded the reciprocal increase of the phagocytosis process. Equally important, we show Mtb induces the early expression of miR-142-3p and partially down-regulates N-Wasp protein levels in both the murine J774A.1 cell line and primary human Mφs. As proof of principle, the partial siRNA-mediated knock down of N-Wasp resulted in a decrease of Mtb intake by human Mφs, reflected in lower levels of colony-forming units (CFU) counts over time. We therefore propose the modulation of miRNAs as a novel strategy in mycobacterial infection to control factors involved in actin filament assembly and other early events of phagolysosome biogenesis.

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  • miR-142-3p targets N-wasp, an actin-binding protein regulating actin dynamics during bacterial uptake.

    “miR-142–3p targets N-wasp, an actin-binding protein regulating actin dynamics during bacterial uptake [145,198].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [145]

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Authors
Bettencourt, P., Marion, S., Pires, D., Santos, L. F., Lastrucci, C., Carmo, N., Blake, J., Benes, V., Griffiths, G., Neyrolles, O., Lugo-Villarino, G., & Anes, E.
Affiliations
  • University of Lisbon (PT)
  • Centre National de la Recherche Scientifique (FR)
  • European Molecular Biology Laboratory (DE)
  • University of Oslo (NO)
Corresponding author
Anes, Elsa
Venue
Frontiers in Cellular and Infection Microbiology
Published
2013
Volume
3
Pages
19-19
ISSN
2235-2988 (ISSN-L)
OpenAlex
W2027751052
Cited by
84
References
4
Citations by year
2026: 5 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 8 · 2021: 15 · 2020: 10 · 2019: 7 · 2018: 8 · 2017: 7 · 2016: 6 · 2015: 2 · 2014: 4 · 2013: 2
FWCI
3.40
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Cellular and Infection Microbiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • London School of Hygiene and Tropical Medicine
  • Fondation pour la Recherche Médicale
  • Centre National de la Recherche Scientifique
  • Fundação para a Ciência e a Tecnologia (PTDC/BIA-BCM/102123/2008)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
Mycobacterium tuberculosis, Mycobacterium smegmatis, microRNA, miR-142-3p, N-WASP, actin-binding proteins, phagocytosis, macrophages, phagolysosome biogenesis, actin filament assembly, host-pathogen interaction, bacterial virulence, J774A.1 macrophages
MeSH terms
Animals, Cells, Cultured, Humans, Mycobacterium tuberculosis, Phagocytosis, Mycobacterium smegmatis, Gene Expression Profiling, MicroRNAs, Wiskott-Aldrich Syndrome Protein, Neuronal, Mice, Host-Pathogen Interactions

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