Multi-platform evidence of GSDMD-dependent pyroptosis in malaria with a potential role for TLR7
Frontiers in Immunology·
- DOI
- 10.3389/fimmu.2026.1862560
- PMID
- —
- PMCID
- —
- OpenAlex
- —
- Study type
- Journal article
- Publisher
- Frontiers Media SA
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The study addresses macrophage-associated inflammation in malaria and identifies TLR7-mediated regulation of pyroptosis as a potential area for further investigation.
Structured evidence summary
Research question
The study investigated pyroptosis pathways in splenic macrophages during Plasmodium infection and whether a TLR7 agonist could regulate that process.
Study design
An integrated study combining clinical transcriptomic analysis, a Plasmodium yoelii-infected mouse model, and in vitro macrophage assays.
Population and setting
The clinical component analyzed transcriptomic data associated with malaria patients; experimental components used P. yoelii-infected mice and macrophage cultures exposed to infected red blood cell lysates.
Main findings
Core pyroptosis genes GSDMD and CASP1/4/5 were significantly upregulated in clinical samples and correlated with myeloid expansion. P. yoelii infection was associated with canonical and non-canonical GSDMD-related pyroptosis in splenic macrophages, while infected red blood cell lysates induced Caspase-1/11 and GSDMD cleavage, membrane perforation, and inflammatory efflux in vitro. R848 administration was associated with reduced pyroptotic signaling, with a particularly strong effect on the Caspase-11/GSDMD non-canonical pathway.
Public-health relevance
The study addresses macrophage-associated inflammation in malaria and identifies TLR7-mediated regulation of pyroptosis as a potential area for further investigation.
Important limitations
The supplied single-article abstract does not provide explicit limitations. This summary is limited to the supplied abstract and bibliographic metadata and requires the original paper for decision-grade interpretation.
GIDS interpretation
The article is discoverable in GIDS through the topics of malaria and treatment. This classification provides topical context only and does not connect the study to a live surveillance signal.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 5 auditable classifier relationships to diseases, places, topics, and study design.