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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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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MicroRNAs as Regulators of Phagocytosis
Gierlikowski, W., & Gierlikowska, B. (2022) · Cells · doi:10.3390/cells11091380 · Cited by 25 · see citing works
- 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
- ORCID
- Venue
- Frontiers in Cellular and Infection Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 3
- Pages
- 19-19
- ISSN
- 2235-2988 (ISSN-L)
- PMC
- PMC3672780
- 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
- gold
- doi.org
- 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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