Inmunidad frente a hongos

review

The immune response to fungal infections
Shmuel Shoham1 and Stuart M. Levitz2 Section of Infectious Diseases, Washington Hospital Center, Washington, DC, and 2Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA, USA
1

Summary
During the past two decades, invasive fungal infections have emerged as a major threat to immunocompromisedhosts. Patients with neoplastic diseases are at significant risk for such infections as a result of their underlying illness and its therapy. Aspergillus, Candida, Cryptococcus and emerging pathogens, such as the zygomycetes, dark walled fungi, Trichosporon and Fusarium, are largely opportunists, causing infection when host defences are breached. The immune response varies with respect to the fungalspecies and morphotype encountered. The risk for particular infections differs, depending upon which aspect of immunity is impaired. This article reviews the current understanding of the role and relative importance of innate and adaptive immunity to common and emerging fungal pathogens. An understanding of the host response to these organisms is important in decisions regarding use of currentlyavailable antifungal therapies and in the design of new therapeutic modalities. Keywords: aspergillosis, candida, cryptococcosis, T cells, dendritic cells.

Overview
With the increasing number of immune compromised patients, fungi have emerged as major causes of human disease. These pathogens are largely opportunists, causing infection when host defences are breached. In this regard, patientswith neoplasms are particularly at risk due to their immunocompromise, which can be a consequence of either their underlying malignancy and/or the treatment for their disease. Of the over 100 000 fungal species in existence, only a small percentage is known to cause human infection. Risk factors for systemic candidiasis include presence of intravascular catheters, receipt of broad-spectrumantibiotics, injury to the gastrointestinal mucosa and neutropenia. Patients

Correspondence: Stuart M. Levitz, MD, Section of Infectious Diseases. Room X626, 650 Albany Street, Boston, MA 02118, USA. E-mail: slevitz@bu.edu

with haematological or solid malignancies and transplant recipients are especially vulnerable. Mucosal candidiasis also occurs in such patients and in those with Acquired ImmuneDeficiency Syndrome (AIDS). Cryptococcosis predominantly affects persons with advanced AIDS, lymphoid and haematological malignancies and transplant recipients. Filamentous fungi, including species of Aspergillus and Fusarium, the Zygomycetes, and the dark walled fungi, generally cause invasive disease in neutropenic hosts and solid organ transplant recipients. At highest risk are patients withprolonged and profound neutropenia after treatment with highly cytotoxic chemotherapy for haematological malignancies and recipients of haematopoietic stem cell transplantation (HSCT). In the latter group, infections with filamentous fungi are increasingly encountered during the post engraftment period. In this article, we will discuss the host response to the pathogenic fungi most likely to infectoncology patients. The immune response varies with respect to the fungal species encountered. The relative importance of specific innate and adaptive defence mechanisms differs, depending upon the organism and anatomical site of infection (Table I). Within a species, the fungal morphotype (e.g. yeast, pseudohyphae and hyphae of Candida albicans) may be an important determinant of the host response.Whereas yeasts and spores are often effectively phagocytosed, the larger size of hyphae precludes effective ingestion. Pathogenic fungi have developed mechanisms to elude and subvert host defences. Some fungi have evolved as intracellular parasites and can survive within phagocytes by using them to evade fungal killing and to disseminate throughout the host. Major characteristics of the immune...