Fungal cell wall polysaccharides β-(1, 3)-glucan and α-(1, 3)-glucan activate the Wnt/β-catenin pathway in human DCs.

A group from Institut National de la Santé et de la Recherche Médicale, Centre de Recherché des Cordeliers, Sorbonne Université, Université de Paris, France, etc. has reported that C-type lectins are necessary in induction of the Wnt/β-catenin pathway and fungal cell wall polysaccharides β-(1, 3)-glucan and α-(1, 3)-glucan, but not chitin, activate the Wnt/β-catenin pathway in human DCs.
https://journals.asm.org/doi/10.1128/mBio.02824-21

Aspergillus fumigatus is an omnipresent airborne fungal pathogen. Although inhaled conidia are usually eliminated in healthy individuals, they may cause hypersensitization, severe asthma with fungal sensitization, allergic bronchopulmonary aspergillosis, colonization of altered respiratory epithelium, and aspergilloma in existing pulmonary lesions.

Innate immune cells, including macrophages, dendritic cells (DCs), and neutrophils, are involved in antifungal activity against A. fumigatus. Upon fungal encounter, DCs engage their various pattern recognition receptors (PRRs) to recognize the evading pathogen. These A. fumigatus-educated DCs subsequently instruct distinct CD4+ T-cell polarization like Th1, Th2, Th17, and FoxP3+ regulatory T cells (Tregs). Among these, Th2 and Th17 responses are nonprotective for Aspergillus infection. On the other hand, Th1 cells have a major role for the induction of protective immune responses. Although Tregs are immunosuppressive and promote chronic and persistent infection, they are also critical for preventing inflammation-associated tissue damage. Therefore, the balance between Th1 and Treg responses is critical for the protective immune response against A. fumigatus.

Recent studies have demonstrated the involvement of Wnt/β-catenin pathway for the induction of tolerogenic functions in DCs and promotion of Treg responses via various anti-inflammatory mechanisms, like expression of IL-10, transforming growth factor beta (TGF-β), and retinoic acid.

By using A. fumigatus as a model, it was shown that fungal species activate the Wnt/β-catenin pathway in human DCs, along with the secretion of Wnt ligands Wnt1 and Wnt7a. Inhibition of the Wnt pathway resulted in decreased DC maturation and selective inhibition of anti-inflammatory cytokine IL-10 without affecting the secretion of most of the proinflammatory cytokines. Abrogation of the Wnt/β-catenin pathway in DCs also led to reduced Treg polarization without altering the polarization of other CD4+ T-cell subsets.

It was also found that C-type lectins are involved in induction of the β-catenin pathway and A. fumigatus’s cell wall polysaccharides β-(1, 3)-glucan and α-(1, 3)-glucan, but not chitin, activate the β-catenin pathway in human DCs.

where, CA=unstimulated, SC=stimulated with swollen conidia