Hypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on the Candida albicans Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling

Abstract

Animal, plant, and fungal cells occupy environments that impose changes in oxygen tension. Consequently, many species have evolved mechanisms that permit robust adaptation to these changes. The fungal pathogen Candida albicans can colonize hypoxic (low oxygen) niches in its human host, such as the lower gastrointestinal tract and inflamed tissues, but to colonize its host, the fungus must also evade local immune defenses. We reveal, for the first time, a defined link between hypoxic adaptation and immune evasion in C. albicans. As this pathogen adapts to hypoxia, it undergoes changes in cell wall structure that include masking of β-glucan at its cell surface, and it becomes better able to evade phagocytosis by innate immune cells. We also define the signaling mechanisms that mediate hypoxia-induced β-glucan masking, showing that they are dependent on mitochondrial signaling and the cAMP-protein kinase pathway. Therefore, hypoxia appears to trigger immune evasion in this fungal pathogen.

mSphere of Influence: Positive Research Culture Enables Excellence and Innovation

“…We all continue to work in this space, contributing to a broader understanding of the many interacting signals that drive titanization (13). It has also served as an example for others facing similar competitive choices in our field (14)(15)(16)(17).…”

A novel genetic circuitry governing hypoxic metabolic flexibility, commensalism and virulence in the fungal pathogen Candida albicans

“…Hypoxia is also an important cue that influences the host-fungal pathogens interaction. When oxygen is depleted, C. albicans cells mask their ß-glucans from the cell wall as a strategy to attenuate phagocytic recognition and uptake [11]. At the infection sites, C. albicans promotes the recruitment and the infiltration of polymorphonuclear leukocytes which consequently generate a hypoxic microenvironment that induces fungal cell masking and evasion of the immune surveillance [11].…”

Ifu5, a WW domain‐containing protein interacts with Efg1 to achieve coordination of normoxic and hypoxic functions to influence pathogenicity traits inCandida albicans

“…As a consequence, C. albicans is able to impede its clearance by evading recognition by the polymorphonuclear leukocytes, pointing to the contribution of hypoxic niches in enhancing virulence (Lopes et al, 2018;Pradhan et al, 2018). As a consequence, C. albicans is able to impede its clearance by evading recognition by the polymorphonuclear leukocytes, pointing to the contribution of hypoxic niches in enhancing virulence (Lopes et al, 2018;Pradhan et al, 2018).…”

“…The link between C. albicans ability to adapt to hypoxia with its pathogenesis is reinforced by the observation that hypoxic conditions enable C. albicans to establish a successful infection by inducing the masking of cell wall β-glucan. As a consequence, C. albicans is able to impede its clearance by evading recognition by the polymorphonuclear leukocytes, pointing to the contribution of hypoxic niches in enhancing virulence (Lopes et al, 2018;Pradhan et al, 2018). Additionally, the ability of this fungal pathogen to undergo the bud-tohyphae transition and form biofilms in response to hypoxia also permits this pathogen to colonise hypoxic niches in the human host.…”