ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Cord factor and peptidoglycan recapitulate the Th17-promoting adjuvant activity of mycobacteria through mincle/CARD9 signaling and the inflammasome.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 134 citations in OpenAlex.
- Mincle-dependent Th17 adjuvanticity requires TNFR1 signaling in myeloid cells.Frontiers in immunology · 2026Article
- Foreign epitope-specific regulatory T cells respond robustly to vaccination and limit Th1 differentiation by conventional T cells specific for the same epitope.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Immunopathogenesis of tuberculosis: cellular mechanisms and immune modulation.Veterinary research · 2025Review
- Precision Adjuvant Strategies in Vaccine Development for Substance Use Disorders: Variability and Mechanistic Insights.Pharmaceutics · 2025Review
- Immunization with Complete Freund's Adjuvant Reveals Trained Immunity-like Features in A/J Mice.Vaccines · 2025Article
- Trimming the fat: a brief review of lipids at the host-pathogen interface.Infection and immunity · 2025Review
- Postbiotics: As a Promising Tools in the Treatment of Celiac Disease.Probiotics and antimicrobial proteins · 2025Review
- The soil Mycobacterium sp. promotes health and longevity through different bacteria-derived molecules in Caenorhabditis elegans.Aging cell · 2025Article
- The Dectin-1 and Dectin-2 clusters: C-type lectin receptors with fundamental roles in immunity.EMBO reports · 2024Review
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- Vaccines and Dementia: Part I. Non-Specific Immune Boosting with BCG: History, Ligands, and Receptors.Journal of Alzheimer's disease : JAD · 2024Review
- Vaccines and Dementia: Part II. Efficacy of BCG and Other Vaccines Against Dementia.Journal of Alzheimer's disease : JAD · 2024Review
- A nod to the bond between NOD2 and mycobacteria.PLoS pathogens · 2023Review
- Targeting of MALT1 May Improve Functional Recovery and Attenuate Microglia M1 Polarization-Mediated Neuroinflammation During Spinal Cord Injury.Molecular neurobiology · 2023Article
- Identification of D-arabinan-degrading enzymes in mycobacteria.Nature communications · 2023Article
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- TH17 cells promote CNS inflammation by sensing danger signals via Mincle.Nature communications · 2022Article
- Fungal microbiome in inflammatory bowel disease: a critical assessment.The Journal of clinical investigation · 2022Review
- Mycobiota and C-Type Lectin Receptors in Cancers: Know thy Neighbors.Frontiers in microbiology · 2022Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 9 institutions in 3 countries.
Funding
Abstract
Although adjuvants are critical vaccine components, their modes of action are poorly understood. In this study, we investigated the mechanisms by which the heat-killed mycobacteria in CFA promote Th17 CD4(+) T cell responses. We found that IL-17 secretion by CD4(+) T cells following CFA immunization requires MyD88 and IL-1β/IL-1R signaling. Through measurement of Ag-specific responses after adoptive transfer of OTII cells, we confirmed that MyD88-dependent signaling controls Th17 differentiation rather than simply production of IL-17. Additional experiments showed that CFA-induced Th17 differentiation involves IL-1β processing by the inflammasome, as mice lacking caspase-1, ASC, or NLRP3 exhibit partially defective responses after immunization. Biochemical fractionation studies further revealed that peptidoglycan is the major component of heat-killed mycobacteria responsible for inflammasome activation. By assaying Il1b transcripts in the injection site skin of CFA-immunized mice, we found that signaling through the adaptor molecule caspase activation and recruitment domain 9 (CARD9) plays a major role in triggering pro-IL-1β expression. Moreover, we demonstrated that recognition of the mycobacterial glycolipid trehalose dimycolate (cord factor) by the C-type lectin receptor mincle partially explains this CARD9 requirement. Importantly, purified peptidoglycan and cord factor administered in mineral oil synergized to recapitulate the Th17-promoting activity of CFA, and, as expected, this response was diminished in caspase-1- and CARD9-deficient mice. Taken together, these findings suggest a general strategy for the rational design of Th17-skewing adjuvants by combining agonists of the CARD9 pathway with inflammasome activators.
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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.