Fungal Invasion of Normally Non-Phagocytic Host Cells

Scott G Filler,Donald C Sheppard

doi:10.1371/journal.ppat.0020129

Abstract

Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research.

Highlights

Pathogenic fungi interact with a variety of host cells during the induction of disease
This review summarizes the results of these investigations (Table 1) and describes gaps in our knowledge of fungal invasion
The results of several studies have led to the development of a model of how C. albicans hyphae induce their own endocytosis by human umbilical vein endothelial cells in vitro

Summary

Introduction

Pathogenic fungi interact with a variety of host cells during the induction of disease. To cross tissue planes and cause invasive disease, these organisms must invade normally nonphagocytic host cells such as epithelial cells and endothelial cells. Two different signal transduction mutants of C. albicans have been discovered to have a reduced capacity to induce endocytosis by oral epithelial cells, even though they have little or no defects in hypha formation. C. albicans hyphae induce endocytosis by human umbilical vein endothelial cells much more efficiently than do blastospores [29].

Results

Conclusion