Evidence map›Paper›PMID 21059889›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2010

TLR9 is actively recruited to Aspergillus fumigatus phagosomes and requires the N-terminal proteolytic cleavage domain for proper intracellular trafficking.

Pia V Kasperkovitz, Michael L Cardenas, Jatin M Vyas

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 74 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Pulmonary Fibrosis and Hypereosinophilia in TLR9Pathogens (Basel, Switzerland) · 2022
    Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. DNA Sensing in the Innate Immune Response.Physiology (Bethesda, Md.) · 2020
    Review
  10. Review
  11. Aspergillus fumigatus and Aspergillosis in 2019.Clinical microbiology reviews · 2019
    Review
  12. CD82 controls CpG-dependent TLR9 signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Complex Negative Regulation of TLR9 by Multiple Proteolytic Cleavage Events.Journal of immunology (Baltimore, Md. : 1950) · 2016
    Article
  18. Article
  19. Review
  20. Dectin-1 Controls TLR9 Trafficking to Phagosomes Containing β-1,3 Glucan.Journal of immunology (Baltimore, Md. : 1950) · 2016
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Pia V KasperkovitzDivision of Infectious Disease, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Michael L Cardenas
Jatin M Vyas
Massachusetts General Hospital · USHarvard University · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Modulation of Dendritic Cell Function by CytomegalovirusK08AI057999 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI VYAS, JATIN M · 2004 to 2008
$605k
NIAID NIH HHS K08 AI-057999NIAID NIH HHS K08 AI057999NIDDK NIH HHS P30 DK043351
6 · The paper itself

Abstract

TLR9 recognizes unmethylated CpG DNA and induces innate immune responses. TLR9 activation is a multistep process requiring proteolytic cleavage and trafficking to endolysosomal compartments for ligand-induced signaling. However, the rules that govern the dynamic subcellular trafficking for TLR9 after pathogen uptake have not been established. In this study, we demonstrate that uptake of Aspergillus fumigatus conidia induced drastic spatial redistribution of TLR9 to the phagosomal membrane of A. fumigatus-containing phagosomes but not to bead-containing phagosomes in murine macrophages. Specific TLR9 recruitment to the fungal phagosome was consistent using A. fumigatus spores at different germination stages and selected mutants affecting the display of Ags on the fungal cell surface. Spatiotemporal regulation of TLR9 compartmentalization to the A. fumigatus phagosome was independent of TLR2, TLR4, and downstream TLR signaling. Our data demonstrate that the TLR9 N-terminal proteolytic cleavage domain was critical for successful intracellular trafficking and accumulation of TLR9 in CpG-containing compartments and A. fumigatus phagosomal membranes. Our study provides evidence for a model in which A. fumigatus spore phagocytosis by macrophages specifically induces TLR9 recruitment to A. fumigatus phagosomes and may thereby mediate TLR9-induced antifungal innate immune responses.

Indexed as

Models, ImmunologicalAnimalsAspergillus fumigatusHEK293 CellsHumansImmunity, InnateIntracellular MembranesMacrophagesMicePhagosomesProtein TransportSignal TransductionSpores, FungalToll-Like Receptor 2Toll-Like Receptor 4Toll-Like Receptor 9TLR2 protein, humanTlr2 protein, mouseTLR4 protein, humanTlr4 protein, mouseTLR9 protein, humanTlr9 protein, mouseToll-Like Receptor 2Toll-Like Receptor 4Toll-Like Receptor 9

Identifiers

PMID21059889
PMCPMC3600358
OpenAlexW2112940475

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.