Neutrophil swarming is crucial for limiting oral mucosal infection by Candida albicans.

Abstract

Oral mucosal colonization by Candida albicans is benign in healthy people but progresses to deeper infection, known as oropharyngeal candidiasis, that may become disseminated when combined with immunosuppression. Cortisone use and neutropenia are risk factors for invasive mucosal fungal infections; however, the mechanisms are poorly understood. Here, we identify in vivo neutrophil functional complexes known as swarms that are crucial for preventing C. albicans epithelial invasion. Anti-Ly6G antibody treatment impaired swarm formation and increased fungal infection depth, confirming the role of neutrophil swarms in limiting C. albicans invasion. Neutrophil swarm function could be disrupted by administration of resolvins, and required BLT1 (leukotriene B4 receptor 1) expression so that administration of a leukotriene synthesis inhibitor reduced neutrophil swarm size permitting C. albicans invasion beyond the basement membrane. Cortisone treatment similarly reduced neutrophil swarming behavior and BLT1 expression and delayed expression of epithelial cytokines and chemokines. Thus, swarm structures have an important function in preventing deep invasion by C. albicans within the oral mucosa and represent a mechanism for increased disease severity under immune deficient clinical settings.