Differences in fungal immune recognition by monocytes and macrophages: N-mannan can be a shield or activator of immune recognition.

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, N-mannan 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.