ArticlePloS one2010
The CD40-autophagy pathway is needed for host protection despite IFN-Γ-dependent immunity and CD40 induces autophagy via control of P21 levels.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 77 citations in OpenAlex.
- Disruption of Epidermal Growth Factor Receptor Signaling in RPE Cells Increases Resistance to Ocular Toxoplasmosis.Investigative ophthalmology & visual science · 2025Article
- Transcriptome analysis of Kunming mice responses to the bite of Xenopsylla cheopis.Parasites & vectors · 2024Article
- Animal Models for Toxoplasma gondii Infection.Current protocols · 2023Article
- The roles of autophagy and mitophagy in corneal pathology: current knowledge and future perspectives.Frontiers in medicine · 2023Review
- Autophagy in protists and their hosts: When, how and why?Autophagy reports · 2023Article
- IFN-γ production by brain-resident cells activates cerebral mRNA expression of a wide spectrum of molecules critical for both innate and T cell-mediated protective immunity to control reactivation of chronic infection withFrontiers in cellular and infection microbiology · 2023Article
- Concurrent Ocular and Cerebral Toxoplasmosis in a Liver Transplant Patient Treated with Anti-CD40 Monoclonal Antibody.Case reports in infectious diseases · 2023Article
- Immunity to Cryptosporidium: Lessons from Acquired and Primary Immunodeficiencies.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Review
- The role of SIRT1 in the process ofFrontiers in microbiology · 2022Article
- Modulation of autophagy as a therapeutic strategy forFrontiers in cellular and infection microbiology · 2022Review
- Impact of IFN-y and CD40 signalling on Toxoplasma gondii cyst formation in differentiated Neuro-2a neuroblastoma cells.Parasite immunology · 2022Article
- Treatment Strategy in Human Ocular Toxoplasmosis: Why Antibiotics Have Failed.Journal of clinical medicine · 2021Review
- A cell-penetrating CD40-TRAF2,3 blocking peptide diminishes inflammation and neuronal loss after ischemia/reperfusion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Recent Advances in the Roles of Autophagy and Autophagy Proteins in Host Cells DuringFrontiers in cell and developmental biology · 2021Review
- The Host Autophagy DuringFrontiers in microbiology · 2020Review
- The role of host autophagy machinery in controllingVirulence · 2019Review
- Toxoplasma gondii induces prolonged host epidermal growth factor receptor signalling to prevent parasite elimination by autophagy: Perspectives for in vivo control of the parasite.Cellular microbiology · 2019Article
- CD40 in Endothelial Cells Restricts Neural Tissue Invasion by Toxoplasma gondii.Infection and immunity · 2019Article
- Epidermal growth factor receptor promotes cerebral and retinal invasion by Toxoplasma gondii.Scientific reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Autophagy degrades pathogens in vitro. The autophagy gene Atg5 has been reported to be required for IFN-γ-dependent host protection in vivo. However, these protective effects occur independently of autophagosome formation. Thus, the in vivo role of classic autophagy in protection conferred by adaptive immunity and how adaptive immunity triggers autophagy are incompletely understood. Employing biochemical, genetic and morphological studies, we found that CD40 upregulates the autophagy molecule Beclin 1 in microglia and triggers killing of Toxoplasma gondii dependent on the autophagy machinery. Infected CD40(-/-) mice failed to upregulate Beclin 1 in microglia/macrophages in vivo. Autophagy-deficient Beclin 1(+/-) mice, mice with deficiency of the autophagy protein Atg7 targeted to microglia/macrophages as well as CD40(-/-) mice exhibited impaired killing of T. gondii and were susceptible to cerebral and ocular toxoplasmosis. Susceptibility to toxoplasmosis occurred despite upregulation of IFN-γ, TNF-α and NOS2, preservation of IFN-γ-induced microglia/macrophage anti-T. gondii activity and the generation of anti-T. gondii T cell immunity. CD40 upregulated Beclin 1 and triggered killing of T. gondii by decreasing protein levels of p21, a molecule that degrades Beclin 1. These studies identified CD40-p21-Beclin 1 as a pathway by which adaptive immunity stimulates autophagy. In addition, they support that autophagy is a mechanism through which CD40-dependent immunity mediates in vivo protection and that the CD40-autophagic machinery is needed for host resistance despite IFN-γ.
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.