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Cited by 61Tuberculosis Research and EpidemiologyMicroRNA in disease regulationMycobacterium research and diagnosis

Mycobacterium tuberculosis Modulates miR-106b-5p to Control Cathepsin S Expression Resulting in Higher Pathogen Survival and Poor T-Cell Activation

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Pires, David, Bernard, Elliott M., Pombo, João Palma, Carmo, Nuno, Fialho, Catarina, Gutierrez, Maximiliano Gabriel, Bettencourt, Paulo, Anes, Elsa·2017·Frontiers in Immunology
DOI 10.3389/fimmu.2017.01819PMC PMC5741618
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Abstract

The success of tuberculosis (TB) bacillus, M. tuberculosis (Mtb), relies on the ability to survive in host cells and escape to immune surveillance and activation. We recently demonstrated that Mtb manipulation of host lysosomal cathepsins in macrophages leads to decreased enzymatic activity and pathogen survival. In addition, while searching for microRNAs involved in post-transcriptional gene regulation during mycobacteria infection of human macrophages, we found that selected microRNAs such as miR-106b-5p were specifically up-regulated by pathogenic mycobacteria. Here, we show that miR-106b-5p is actively manipulated by Mtb to ensure its survival in macrophages. Using an in silico prediction approach, we identified miR-106b-5p with a potential binding to the 3'-untranslated region (3'-UTR) of cathepsin S (CtsS) mRNA. We demonstrated by luminescence-based methods that miR-106b-5p indeed targets CTSS mRNA resulting in protein translation silencing. Moreover, miR-106b-5p gain-of-function experiments lead to a decreased CtsS expression favoring Mtb intracellular survival. By contrast, a miR-106b-5p loss-of-function in infected cells was concomitant with increased CtsS expression, with significant intracellular killing of Mtb and T-cell activation. Modulation of miR-106b-5p did not impact necrosis, apoptosis or autophagy arguing that miR-106b-5p directly targeted CtsS expression as a way for Mtb to avoid exposure to degradative enzymes in the endocytic pathway. Altogether, our data suggest that manipulation of miR-106b-5p as a potential target for host-directed therapy for Mtb infection.

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  • miR-106-5p is upregulated by Mtb infection in macrophages and targets cathepsin S mRNA, decreasing lysosomal activity.

    “miR-106-5p, a microRNA upregulated by Mtb infection in macrophages and targets cathepsin S (CtsS) mRNA, thus decreasing lysosomal activity [136,198].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [136]

    The Results section (‘Mtb Induces the Expression of miR-106b-5p in Human Mø’) reports upregulation during infection, and the Abstract reports that miR-106b-5p targets CtsS mRNA. The cited paper identifies the microRNA as miR-106b-5p, not miR-106-5p, and reports reduced CtsS activity and endolysosomal proteolysis rather than a general decrease in lysosomal activity. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Pires, D., Bernard, E. M., Pombo, J. P., Carmo, N., Fialho, C., Gutierrez, M. G., Bettencourt, P., & Anes, E.
Affiliations
  • University of Lisbon (PT)
  • The Francis Crick Institute (GB)
Corresponding author
Anes, Elsa
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2017-12-18
Volume
8
Pages
1819-1819
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2017.01819
PMC
PMC5741618
OpenAlex
W2772266294
Cited by
61
References
4
Citations by year
2026: 2 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 7 · 2019: 5 · 2018: 3
FWCI
3.16
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Fundação para a Ciência e a Tecnologia (PTDC/BIA-BCM/102123/2008, PTDC/Sau-MII/098024/2008)
  • Francis Crick Institute (Cancer Research UK FC001092, UK Medical Research Council MC_UP_1202/11, FC001092, Wellcome Trust FC001092)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
Keywords
Mycobacterium tuberculosis, miR-106b-5p, cathepsin S, microRNA regulation, host-directed therapy, intracellular survival, macrophages, T cell activation, lysosomal enzymes, post-transcriptional regulation, 3' untranslated region, host-pathogen interaction, tuberculosis

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