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There are multiple overlapping mechanisms for protection against corneal fungal infections. The source of infection is nearly always exogenous and due to environmental molds (e.g., Fusarium and Aspergillus) or cutaneous yeasts (e.g., Candida albicans). Therefore, intact anatomical barriers and effective tear function are crucial first lines of defense. Antimicrobial substances such as lysozyme, lactoferrin, lipocalin, and defensins which are found in tears and/or produced by corneal cells constitute an additional line of defense. Finally, the presence of fungi or fungal products at the corneal surface triggers signaling pathways within resident corneal cells that then activate direct or indirect cellular responses. These include the recruitment of neutrophils and T cells to the site of infection and activation of antifungal mechanisms. Taken as a whole, host defenses at the ocular surface provide a multilayered and overwhelmingly effective shield against fungal keratitis.

The development of mucosal and invasive candidiasis depends upon a variety of innate and acquired risk factors. The number of genes known to be important for immunity against candidiasis has been increasing. Studies of variants of these genes are facilitating our knowledge of host predisposition to infection. Insights gleaned from genetic variants identified in patients with primary immunodeficiency syndromes such as chronic mucocutaneous candidiasis have further aided in this process. This article reviews data from genomic association studies in patients with such syndromes and in broader patient populations. These studies are placed within the framework of our current understanding of antifungal host defenses.

Implantable device infections are an important cause of invasive candidiasis and carry high rates of morbidity and mortality. Central vascular access catheters are by far the most commonly infected type of device. Infections associated with peritoneal dialysis catheters, cardiac devices, prosthetic joints, and other implantable devices are much less common but can have devastating consequences for affected patients. Central to the pathogenesis of these infections is the interplay between altered anatomic barriers due to device implantation, host immune factors, and the tendency of Candida to form biofilms upon inanimate surfaces. Once infection develops, current treatment options nearly always necessitate removal of the device, so major efforts are under way to prevent infection by implementing innovative infection control strategies and developing implants that are less susceptible to biofilm formation. This review focuses on recent developments in our understanding of the epidemiology, pathogenesis, treatment options, and prevention of implant-associated invasive candidiasis.

Development of invasive fungal infection is the result of the complex interaction between fungal and host factors. The outcome of infection, once it has developed, depends upon appropriate use of antifungal therapy, surgical debridement as indicated, and improvement of host defenses. Thus, there have been major efforts for development of new strategies for immunomodulation and augmentation of host defenses in prevention and treatment of invasive mycoses. These modalities include granulocyte and granulocyte-macrophage colony-stimulating factors, interferon-γ, granulocyte transfusions, immunotherapy with infusion of dendritic cells and T cells, anti-heat shock protein 90 monoclonal antibodies, long pentraxin 3, mannose-binding lectin, and deferasirox. Although major strides in our understanding of augmentation of host response to invasive fungal infections are opening up novel avenues of therapy to harness patients’ innate immune systems against these frequently lethal pathogens, well-designed clinical trials are needed to demonstrate safety and efficacy of these new approaches.

Decisions about the prophylactic and empiric use of antifungal agents in immunosuppressed recipients of solid-organ transplants and hematopoietic stem cell transplantation (HSCT) call for up-to-date knowledge regarding which infections are most likely to develop in the populations at risk, but rapidly changing immunosuppressive regimens and the costs of large-scale clinical trials require new ways of gathering these data. Leveraging new clinical data from electronic databases to better understand the changing epidemiology of invasive fungal infection and the patterns of risk factors for adverse effects of antifungal treatment offers a major challenge and opportunity. Evidence-based integration of results generated from traditional prospective clinical trials, clinical and genomic databases, and laboratory-based investigations will enable us to maximize the potential benefits of antifungal agents and reduce their risks.