ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Cutting edge: Nicastrin and related components of γ-secretase generate a peptide epitope facilitating immune recognition of intracellular mycobacteria, through MHC class II-dependent priming of T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice.Cell reports. Medicine · 2021Article
- Inhibition of γ-secretase in adipocytes leads to altered IL-6 secretion and adipose inflammation.Adipocyte · 2020Article
- NOD2/RIG-I ActivatingFrontiers in immunology · 2020Article
- An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice.NPJ vaccines · 2019Article
- Microbial co-infection alters macrophage polarization, phagosomal escape, and microbial killing.Innate immunity · 2018Article
- Plasma Membrane Profiling Reveals Upregulation of ABCA1 by Infected Macrophages Leading to Restriction of Mycobacterial Growth.Frontiers in microbiology · 2016Article
- The role of TGF-β signaling and apoptosis in innate and adaptive immunity in zebrafish: a systems biology approach.BMC systems biology · 2014Article
- BCG vaccine mediated reduction in the MHC-II expression of macrophages and dendritic cells is reversed by activation of Toll-like receptors 7 and 9.Cellular immunology · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Bacillus Calmette-Guérin (BCG), the antituberculosis vaccine, localizes within immature phagosomes of macrophages and dendritic cells (APCs), and avoids lysosomal degradation. BCG-derived antigenic peptides are thus inefficiently processed by APCs, and we investigated alternate mechanisms of Ag processing. Proteomics identified that BCG phagosomes are enriched for nicastrin, APH, and presenilin components of γ-secretase, a multimeric protease. Using an in vitro Ag presentation assay and BCG-infected APCs, we found γ-secretase components to cleave BCG-derived Ag85B to produce a peptide epitope, which, in turn, primed IL-2 release from Ag85B-specific T cell hybridoma. siRNA knockdown or chemical inhibition of γ-secretase components using L685458 decreased the ability of BCG or Mycobacterium tuberculosis-infected APCs to present Ag85B. In addition, L685485 inhibition of γ-secretase led to a decreased ability of BCG-dendritic cells to immunize mice and induce Ag85B-specific CD4 T cells in vivo. Because BCG and M. tuberculosis sequester within APCs preventing immune recognition, γ-secretase components appear to fortuitously process the immunodominant Ag85B, facilitating immune recognition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.