Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans

Author: 

Petra Bacher, Thordis Hohnstein, Eva Beerbaum, Marie Röcker, Matthew G.Blango, Svenja Kaufmann, Jobst Röhmel, Patience Eschenhagen, Claudia Grehn, Kathrin Seidel, Volker Rickerts, Laura Lozza, Ulrik Stervbo, Mikalai Nienen, Nina Babel, Julia Milleck, Mario Assenmacher, Oliver A.Cornely, Alexander Scheffold.
Cell 176, 1–16, March 7, 2019

Abstract: 

Th17 cells provide protection at barrier tissues but may also contribute to immune pathology. The relevance and induction mechanisms of pathologic Th17 responses in humans are poorly understood.

Here, we identify the mucocutaneous pathobiont Candida albicans as the major direct inducer of human anti-fungal Th17 cells. Th17 cells directed against other fungi are induced by cross-reactivity to C. albicans. Intestinal inflammation expands total C. albicans and cross-reactive Th17 cells. Strikingly, Th17 cells cross-reactive to the airborne fungus Aspergillus fumigatus are selectively activated and expanded in patients with airway inflammation, especially during acute allergic bronchopulmonary aspergillosis. This indicates a direct link between protective intestinal Th17 responses against C. albicans and lung inflammation caused by airborne fungi. We identify heterologous immunity to a single, ubiquitous member of the microbiota as a central mechanism for systemic induction of human antifungal Th17 responses and as a potential risk factor for pulmonary inflammatory diseases.