Evidence map›Paper›PMID 20581055›Full record

ArticleThe American journal of pathology2010

TLR9 signaling is required for generation of the adaptive immune protection in Cryptococcus neoformans-infected lungs.

Yanmei Zhang, Fuyuan Wang, Urvashi Bhan, Gary B Huffnagle, Galen B Toews, Theodore J Standiford, Michal A Olszewski

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.8field-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

41 citing papers in PubMed, 60 citations in OpenAlex.

  1. TREM2 drives monocyte-derived macrophage responses tobioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Review
  4. Dendritic Cells: Multifunctional Roles in Host Defenses toJournal of fungi (Basel, Switzerland) · 2023
    Review
  5. Innate Pulmonary Phagocytes and Their Interactions with PathogenicJournal of fungi (Basel, Switzerland) · 2023
    Review
  6. Pulmonary Fibrosis and Hypereosinophilia in TLR9Pathogens (Basel, Switzerland) · 2022
    Article
  7. Influence of Pathogen Carbon Metabolism on Interactions With Host Immunity.Frontiers in cellular and infection microbiology · 2022
    Review
  8. Article
  9. Article
  10. Article
  11. Pulmonary Macrophage and Dendritic Cell Responses toFrontiers in cellular and infection microbiology · 2020
    Review
  12. Article
  13. Article
  14. Interactions of Cryptococcus with Dendritic Cells.Journal of fungi (Basel, Switzerland) · 2018
    Review
  15. Innate Immune Responses toJournal of fungi (Basel, Switzerland) · 2017
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

7 authors at 1 institution in 1 country.

Yanmei ZhangVeterans Affairs Ann Arbor Health System, Ann Arbor, Michigan, USA.
Fuyuan Wang
Urvashi Bhan
Gary B Huffnagle
Galen B Toews
Theodore J Standiford
Michal A Olszewski
University of Michigan · US

Funding

Role of TLR9 in Lung Antibacterial Host DefenseR01HL057243 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI STANDIFORD, THEODORE J. · 1997 to 2011
$3.6M
MACROPHAGE RECRUITMENT/ACTIVATION IN LUNG DEFENSER01HL051082 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TOEWS, GALEN B · 1994 to 2007
$2.5M
MODULATION OF TH1/TH2 RESPONSES BY INNATE IMMUNITYR01HL065912 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HUFFNAGLE, GARY B. · 2000 to 2004
$1.5M
CHEMOKINE RECEPTORS IN IMMUNITY TO C NEOFORMANSR01HL063670 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HUFFNAGLE, GARY B. · 1999 to 2003
$1.1M
TLR9 Mediated Dendritic Cell Responses in Hypersensitivity PneumonitisK08HL094762 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BHAN, URVASHI · 2009 to 2013
$667k
NHLBI NIH HHS HL25243NHLBI NIH HHS HL97456NHLBI NIH HHS K08 HL094762NHLBI NIH HHS K08-HL094762NHLBI NIH HHS R01 HL051082NHLBI NIH HHS R01 HL057243NHLBI NIH HHS R01 HL065912NHLBI NIH HHS R01-HL51082NHLBI NIH HHS R01-HL63670NHLBI NIH HHS R01-HL65912
6 · The paper itself

Abstract

To determine whether TLR9 signaling contributes to the development of the adaptive immune response to cryptococcal infection, wild-type (TLR9+/+) and TLR9 knockout (TLR9-/-) BALB/c mice were infected intratracheally with 10(4) C. neoformans 52D. We evaluated 1) organ microbial burdens, 2) pulmonary leukocyte recruitment, 3) pulmonary and systemic cytokine induction, and 4) macrophage activation profiles. TLR9 deletion did not affect pulmonary growth during the innate phase, but profoundly impaired pulmonary clearance during the adaptive phase of the immune response (a 1000-fold difference at week 6). The impaired clearance in TLR9-/- mice was associated with: 1) significantly reduced CD4(+), CD8+ T cell, and CD19+ B cell recruitment into the lungs; 2) defects in Th polarization indicated by altered cytokine responses in the lungs, lymphonodes, and spleen; and 3) diminished macrophage accumulation and altered activation profile, including robust up-regulation of Arg1 and FIZZ1 (indicators of alternative activation) and diminished induction of inducible nitric oxide synthase (an indicator of classical activation). Histological analysis revealed defects in granuloma formation and increased numbers of intracellular yeast residing within macrophages in the lungs of TLR9-/- mice. We conclude that TLR9 signaling plays an important role in the development of robust protective immunity, proper recruitment and function of effector cells (lymphocytes and macrophages), and, ultimately, effective cryptococcal clearance from the infected lungs.

Indexed as

Lung DiseasesAdaptive ImmunityAnimalsCryptococcosisCryptococcus neoformansCytokinesFemaleHumansMiceMice, Inbred BALB CMice, KnockoutSignal TransductionT-Lymphocytes, Helper-InducerT-Lymphocyte SubsetsToll-Like Receptor 9CytokinesTlr9 protein, mouseToll-Like Receptor 9

Identifiers

PMID20581055
PMCPMC2913381
OpenAlexW1987746874

What OpenQuestion holds

Textmetadata
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.