Protective immunity against Candida albicans in the oral mucosa and systemically

Immunosurveillance of C. albicans in the oral mucosa


As part of the normal microbiota C. albicans colonizes the mucosa of the gastrointestinal and vaginal tract of humans. How the host keeps a stable balance with the fungus to prevent its overgrowth, which might result in infection and inflammation, is not fully clear. CD4+ T cells and in particular the Th17 subset play a pivotal role in this process, as evidenced by individuals with defects in the T cell compartment or the IL-17 pathway. Mechanistic studies were limited so far to in vitro experiments with isolated human cells and to animal models of acute and transient infection with C. albicans, which do not well reflect the situation of commensalism in humans. A new experimental model of persistent colonization of the oral mucosa with C. albicans in normal (non-immunosuppressed or antibiotically treated) hosts allows for the first time to assess the Th17-mediated mechanisms of immunosurveillance in mucosal barrier tissues that maintain stable commensalism.

LEGEND: The IL-17 pathway constitutes a critical mechanism of fungal control. Immunosurveillance of C. albicans commensalism is mediated by IL-17-secreting CD103+ tissue resident memory T cells (left ). Interruption of IL-17 signaling results in a strong increase of fungal colonization in the oral mucosa (right ).


Innate immunity against systemic candidiasis


Systemic infections with C. albicans arise if the fungus crosses the epithelial barrier and reaches internal organs such as kidney and liver via the blood stream. Myeloid cells of the innate immune cells including neutrophils and monocytes play a key role in host defense against systemic candidiasis. They normally reside in the blood circulation but are rapidly recruited into the parenchymal tissue of the infected organs, where they the complement tissue resident subsets of myeloid cells for optimal protection against the fungus. Myeloid cell dynamics and effector functions are tightly regulated by cytokine networks. This project explores the role of interleukin-23 in these processes. Using an experimental model of systemic candidiasis in vivo, we uncovered an unprecedented novel role of IL-23 in promoting myeloid cell viability. Importantly, IL-23-mediated protection of myeloid cells from apoptosis was found to be independent of the IL-23-IL-17 immune axis.

Funding: Swiss National Science Foundation

LEGEND: Neutrophils play a key role in host defence against systemic candidiasis. They closely associate with large C. albicans filaments (left and middle). Neutrophil viability is regulated by the IL-23 cytokine pathway. The t-SNE plot shows IL-23 receptor expression by various myeloid cell populations in the infected kidney (right, orange-red colour)