Cited by 198Tuberculosis Research and EpidemiologyMycobacterium research and diagnosisImmune responses and vaccinations

Cytosolic Access of Mycobacterium tuberculosis: Critical Impact of Phagosomal Acidification Control and Demonstration of Occurrence In Vivo

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Simeone, Roxane, Sayes, Fadel, Song, Okryul, Gröschel, Matthias I., Brodin, Priscille, Brosch, Roland, Majlessi, Laleh·2015·PLOS Pathogens

Abstract

Mycobacterium tuberculosis (Mtb) uses efficient strategies to evade the eradication by professional phagocytes, involving--as recently confirmed--escape from phagosomal confinement. While Mtb determinants, such as the ESX-1 type VII secretion system, that contribute to this phenomenon are known, the host cell factors governing this important biological process are yet unexplored. Using a newly developed flow-cytometric approach for Mtb, we show that macrophages expressing the phagosomal bivalent cation transporter Nramp-1, are much less susceptible to phagosomal rupture. Together with results from the use of the phagosome acidification inhibitor bafilomycin, we demonstrate that restriction of phagosomal acidification is a prerequisite for mycobacterial phagosomal rupture and cytosolic contact. Using different in vivo approaches including an enrichment and screen for tracking rare infected phagocytes carrying the CD45.1 hematopoietic allelic marker, we here provide first and unique evidence of M. tuberculosis-mediated phagosomal rupture in mouse spleen and lungs and in numerous phagocyte types. Our results, linking the ability of restriction of phagosome acidification to cytosolic access, provide an important conceptual advance for our knowledge on host processes targeted by Mtb evasion strategies.

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  • Due to the absence of ESX-1, BCG does not gain access to the host cell cytosol and thus lacks the induction of certain immune signaling pathways.

    “Due to the absence of ESX-1, BCG does not gain access to the host cell cytosol and thus lacks the induction of certain immune signaling pathways (74,86).”

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Authors
Simeone, R., Sayes, F., Song, O., Gröschel, M. I., Brodin, P., Brosch, R., & Majlessi, L.
Affiliations
  • Institut Pasteur (FR)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
  • Brosch, Roland
  • Majlessi, Laleh
Venue
PLOS Pathogens
Published
2015-02-06
Volume
11
Issue
2
Pages
e1004650
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
OpenAlex
W1992799735
Cited by
198
References
77
Citations by year
2026: 6 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 15 · 2021: 16 · 2020: 21 · 2019: 25 · 2018: 26 · 2017: 25 · 2016: 26 · 2015: 15
FWCI
23.88
Type
journal article
Language
en
Open access
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
Funders
  • Jan Kornelis de Cock Stichting
  • Equipex
  • European Commission (260872, 241745)
  • Fondation pour la Recherche Médicale (DEQ20130326471)
  • FP7 Ideas: European Research Council (260901)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
Mycobacterium tuberculosis, phagosome acidification, bafilomycin, macrophages, host-pathogen interaction, phagosome escape, ESX-1 secretion system
MeSH terms
Natural Resistance-associated Macrophage Protein 1, Animals, Humans, Hydrogen-Ion Concentration, Macrophages, Mice, Mutant Strains, Mycobacterium tuberculosis, Phagosomes, Tuberculosis, Leukocyte Common Antigens, Cation Transport Proteins, Cell Line, Tumor, Mice, Bacterial Secretion Systems

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