We designed experiments to assess whether fungal cell wall mannans function as an immune shield or an
immune agonist. Fungal cell wall β-(1,3)-glucan normally plays a major and dominant role in immune activation.
The outer mannan layer has been variously described as an immune shield, because it has the potential to mask
the ...
We designed experiments to assess whether fungal cell wall mannans function as an immune shield or an
immune agonist. Fungal cell wall β-(1,3)-glucan normally plays a major and dominant role in immune activation.
The outer mannan layer has been variously described as an immune shield, because it has the potential to mask
the underlying β-(1,3)-glucan, or an immune activator, as it also has the potential to engage with a wide range of
mannose detecting PRRs. To resolve this conundrum we examined species-specific differences in host immune
recognition in the och1Δ N-mannosylation-deficient mutant background in four species of yeast-like fungi.
Irrespective of the fungal species, the cytokine response (TNFα and IL-6) induced by the och1Δ mutants in
human monocytes was reduced compared to that of the wild type. In contrast, TNFα production induced by
och1Δ was increased, relative to wild type, due to increased β-glucan exposure, when mouse or human
macrophages were used. These observations suggest that N-mannan is not a major PAMP for
macrophages and that in these cells mannan does shield the fungus from recognition of the inner
cell wall β-glucan. However, Nmannan is a significant inducer of cytokine for monocytes. Therefore
the metaphor of the fungal “mannan shield” can only be applied to some, but not all, myeloid
cells used in immune profiling experiments of fungal species