ArticlePLoS pathogens2011
A cardinal role for cathepsin d in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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.
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.
Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- Amplified inflammatory and immune responses in viral-associated pulmonary aspergillosis.Frontiers in cellular and infection microbiology · 2026Article
- Review
- A fluorogenic, peptide-based probe for the detection of Cathepsin D in macrophages.Communications chemistry · 2023Article
- The role of lysosomes in metabolic and autoimmune diseases.Nature reviews. Nephrology · 2023Review
- Transient increase in atherosclerotic plaque macrophage content followingFrontiers in cellular and infection microbiology · 2023Article
- Tissue-resident immunity in the lung: a first-line defense at the environmental interface.Seminars in immunopathology · 2022Review
- Spatial localization of cathepsins: Implications in immune activation and resolution during infections.Frontiers in immunology · 2022Review
- Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis.eLife · 2021Article
- Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases.Advances in experimental medicine and biology · 2021Article
- Modulation of Cystatin C in Human Macrophages Improves Anti-Mycobacterial Immune Responses toFrontiers in immunology · 2021Article
- Insights into theJournal of fungi (Basel, Switzerland) · 2020Article
- Developing Novel Host-Based Therapies Targeting Microbicidal Responses in Macrophages and Neutrophils to Combat Bacterial Antimicrobial Resistance.Frontiers in immunology · 2020Review
- The Role of Macrophages inFrontiers in immunology · 2020Review
- CSF Levels of Elongation Factor Tu Is Associated With Increased Mortality in Malawian Adults WithFrontiers in cellular and infection microbiology · 2020Article
- Cathepsins in Bacteria-Macrophage Interaction: Defenders or Victims of Circumstance?Frontiers in cellular and infection microbiology · 2020Review
- TRPML Cation Channels in Inflammation and Immunity.Frontiers in immunology · 2020Review
- Alveolar Macrophage Apoptosis-associated Bacterial Killing Helps Prevent Murine Pneumonia.American journal of respiratory and critical care medicine · 2019Article
- Pellino-1 Regulates Immune Responses toFrontiers in immunology · 2019Article
- Integrative Physiology of Pneumonia.Physiological reviews · 2018Review
- HIV gp120 in the Lungs of Antiretroviral Therapy-treated Individuals Impairs Alveolar Macrophage Responses to Pneumococci.American journal of respiratory and critical care medicine · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D(-/-) hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function.
Indexed as
Identifiers
What OpenQuestion holds
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.