In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice

Park, Hyun Jung; Lee, Sung Won; Park, Yun Hoo; Kim, Tae-Cheol; Lee, Sujin; Lee, Seyeong; Van Kaer, Luc; Hong, Seokmann

doi:10.3390/molecules28155779

Cited by 4 publications

(2 citation statements)

References 40 publications

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“…First, there are likely substantial differences in the relative availability of TLR2 binding sites between fragmented S. cerevisiae -derived cell walls (zymosan) and intact C. albicans yeasts 33 . Secondly, it is possible that complex regulatory mechanisms exist in vivo that dampen the TLR-mediated effects 34 ; this would also explain why others have observed that zymosan injection in vivo slightly increases intracellular TNF in splenic macrophages 35 . Thirdly, C. albicans interacts with multiple other host receptors in vivo, such as NLRP3, CR3, and mannose receptors, all of which have the potential to influence trained immunity 36 .…”

Section: Discussionmentioning

confidence: 99%

Dectin-1 ligands produce distinct training phenotypes in human monocytes through differential activation of signaling networks

Cheng,

Farrell,

Fenn

et al. 2024

Sci Rep

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Cells of the innate immune system retain memory of prior exposures through a process known as innate immune training. β-glucan, a Dectin-1 ligand purified from the Candida albicans cell wall, has been one of the most widely utilized ligands for inducing innate immune training. However, many Dectin-1 ligands exist, and it is not known whether these all produce the same phenotype. Using a well-established in vitro model of innate immune training, we compared two commercially available Dectin-1 agonists, zymosan and depleted zymosan, with the gold standard β-glucan in the literature. We found that depleted zymosan, a β-glucan purified from Saccharomyces cerevisiae cell wall through alkali treatment, produced near identical effects as C. albicans β-glucan. However, untreated zymosan produced a distinct training effect from β-glucans at both the transcript and cytokine level. Training with zymosan diminished, rather than potentiated, induction of cytokines such as TNF and IL-6. Zymosan activated NFκB and AP-1 transcription factors more strongly than β-glucans. The addition of the toll-like receptor (TLR) ligand Pam3CSK4 was sufficient to convert the training effect of β-glucans to a phenotype resembling zymosan. We conclude that differential activation of TLR signaling pathways determines the phenotype of innate immune training induced by Dectin-1 ligands.

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Section: Discussionmentioning

confidence: 99%

Dectin-1 ligands produce distinct training phenotypes in human monocytes through differential activation of signaling networks

Cheng,

Farrell,

Fenn

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…First, there are likely substantial differences in the relative availability of TLR2 binding sites between fragmented S. cerevisiae -derived cell walls (zymosan) and intact C. albicans yeasts (38). Secondly, it is possible that complex regulatory mechanisms exist in vivo that dampen the TLR-mediated effects (39); this would also explain why others have observed that zymosan injection in vivo slightly increases intracellular TNF in splenic macrophages (40). Thirdly, C. albicans interacts with multiple other host receptors in vivo , such as NLRP3, CR3, and mannose receptors, all of which have the potential to influence trained immunity (41).…”

Section: Discussionmentioning

confidence: 99%

Dectin-1 ligands produce distinct training phenotypes in human monocytes through differential activation of signaling networks

Cheng,

Farrell,

Fenn

et al. 2023

Preprint

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Cells of the innate immune system retain memory of prior exposures through a process known as innate immune training. β-glucan, a Dectin-1 ligand purified from theCandida albicanscell wall, has been one of the most widely u:lized and well-characterized ligands for inducing innate immune memory. However, many Dectin-1 agonists exist, and it is not known whether all Dectin-1 ligands produce the same phenotype. Using a well-establishedin vitromodel of trained immunity, we compared two commercially available Dectin-1 agonists, zymosan and depleted zymosan, with the gold standard β-glucan in the literature. We found that depleted zymosan, a β-glucan purified fromSaccharomyces cerevisiaecell wall through alkali treatment, produced near identical training effects asC. albicansβ-glucan. However, untreated zymosan produced a distinct training effect from β-glucans at both the transcript and cytokine level. Training with zymosan diminished, rather than potentiated, induction of key cytokines such as TNF, IL-12, and IL-6. Zymosan activated NF𝓀B and AP-1 transcription factors more strongly than β-glucans. The addition of the toll-like receptor (TLR) ligand Pam3CSK4 was sufficient to convert the training effect of β-glucans to a phenotype resembling training with zymosan. We conclude that differential activation of TLR signaling pathways determines the phenotype of innate immune training induced by Dectin-1. These findings bring clarity to the specific question of which Dectin-1 agonists produce prototypical training effects and provide broader insight into how signaling networks regulate innate immune training.

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Therapeutic potential of natural killer cells in neuroimmunological diseases

Zhang,

Lin,

Yang

et al. 2024

Biomedicine & Pharmacotherapy

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In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice

Cited by 4 publications

References 40 publications

Dectin-1 ligands produce distinct training phenotypes in human monocytes through differential activation of signaling networks

Dectin-1 ligands produce distinct training phenotypes in human monocytes through differential activation of signaling networks

Dectin-1 ligands produce distinct training phenotypes in human monocytes through differential activation of signaling networks

Therapeutic potential of natural killer cells in neuroimmunological diseases

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