Multiplexed Quantitation of Intraphagocyte Mycobacterium tuberculosis Secreted Protein Effectors
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The pathogenic potential of Mycobacterium tuberculosis largely depends on ESX secretion systems exporting members of the multigenic Esx, Esp, and PE/PPE protein families. To study the secretion and regulation patterns of these proteins while circumventing immune cross-reactions due to their extensive sequence homologies, we developed an approach that relies on the recognition of their MHC class II epitopes by highly discriminative T cell receptors (TCRs) of a panel of T cell hybridomas. The latter were engineered so that each expresses a unique fluorescent reporter linked to specific antigen recognition. The resulting polychromatic and multiplexed imaging assay enabled us to measure the secretion of mycobacterial effectors inside infected host cells. We applied this novel technology to a large panel of mutants, clinical isolates, and host-cell types to explore the host-mycobacteria interplay and its impact on the intracellular bacterial secretome, which also revealed the unexpected capacity of phagocytes from lung granuloma to present mycobacterial antigens via MHC class II.
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A technology termed MASSTT was developed to explore the intra-host cell secretion profiles of various mycobacterial strains via fluorescence-mediated detection of specific M. tuberculosis MHC-II epitopes by highly discriminative T cell hybridomas.
“Recently, a technology termed multiplexed analysis of substrate secretion by transduced T cell hybridomas (MASSTT) was developed to explore the intra-host cell secretion profiles of various mycobacterial strains via fluorescencemediated detection of specific M. tuberculosis major histocompatibility complex class II (MHC-II) epitopes by highly discriminative T cell hybridomas (84).”
From ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins (2019) · cites this paper as [84]
Strains of different phylogenetic lineages showed distinct secretion levels of Ag85B proteins in a preliminary set of M. tuberculosis strains by the MASSTT assay, information that needs to be confirmed with a larger strain collection.
“Interestingly, strains of different phylogenetic lineages showed distinct secretion levels of Ag85B proteins in a preliminary set of M. tuberculosis strains by the MASSTT assay (84), information that needs to be confirmed with a larger strain collection.”
From ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins (2019) · cites this paper as [84]
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ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins
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- Authors
- Sayes, F., Blanc, C., Ates, L. S., Deboosere, N., Orgeur, M., Le Chevalier, F., Gröschel, M. I., Frigui, W., Song, O.-R., Lo-Man, R., Brossier, F., Sougakoff, W., Bottai, D., Brodin, P., Charneau, P., Brosch, R., & Majlessi, L.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Institut Pasteur (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- University of Pisa (IT)
- Corresponding author
- Majlessi, Laleh
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 23
- Issue
- 4
- Pages
- 1072-1084
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5946722
- OpenAlex
- W2802668680
- Cited by
- 36
- References
- 59
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 4
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
- Funders
- Institut Pasteur (PTR 441)
- European Regional Development Fund (12001407 D-AL)
- Fondation pour la Recherche Médicale (SPF20160936136, DEQ20130326471)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- Mycobacterium tuberculosis, ESX secretion system, PE/PPE proteins, MHC class II epitopes, T cell receptor recognition, T cell hybridomas, fluorescent reporter, multiplexed imaging, host-pathogen interaction, phagocytes, lung granulomas, antigen presentation, bacterial secretome
- MeSH terms
- Animals, Histocompatibility Antigens Class II, Mycobacterium tuberculosis, Phagocytes, Tuberculosis, Pulmonary, Granuloma, Respiratory Tract, Epitopes, T-Lymphocyte, Cell Line, Tumor, Mice, Bacterial Secretion Systems
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