The cell wall provides a major physical interface between fungal pathogens and their
mammalian host. This extracellular armour is critical for fungal cell homeostasis and survival.
Fungal-specific cell wall moieties, such as β-1,3-glucan, are recognised as pathogen-associated molecular patterns (PAMPs) that activate immune-mediated ...
The cell wall provides a major physical interface between fungal pathogens and their
mammalian host. This extracellular armour is critical for fungal cell homeostasis and survival.
Fungal-specific cell wall moieties, such as β-1,3-glucan, are recognised as pathogen-associated molecular patterns (PAMPs) that activate immune-mediated clearance mechanisms. We have reported that the opportunistic human fungal pathogen, Candida albicans, masks β-1,3-glucan following exposure to lactate, hypoxia or iron depletion.
However, the precise mechanism(s) by which C. albicans masks β-1,3-glucan have
remained obscure. Here we identify a secreted exoglucanase, Xog1, that is induced in
response to lactate or hypoxia. Xog1 functions downstream of the lactate-induced β-glucan
“masking” pathway to promote β-1,3-glucan “shaving”. Inactivation of XOG1 blocks most, but
not all β-1,3-glucan masking in response to lactate, suggesting that other activities contribute
to this phenomenon. Nevertheless, XOG1 deletion attenuates the lactate-induced reductions
in phagocytosis and cytokine stimulation normally observed for wild type cells. We also
demonstrate that the pharmacological inhibition of exoglucanases undermines β-glucan
shaving, enhances the immune visibility of the fungus, and attenuates its virulence. Our
study establishes a new mechanism underlying environmentally-induced PAMP remodelling
that can be manipulated pharmacologically to influence immune recognition and infection
outcomes.