Candida and Host Determinants of Susceptibility to Invasive Candidiasis

Michail S Lionakis,Mihai G Netea,Joseph Heitman

doi:10.1371/journal.ppat.1003079

Abstract

Candida is the most common human fungal pathogen and the cause of invasive candidiasis, the fourth leading cause of nosocomial bloodstream infection in the United States with an estimated annual cost of ∼US$2 billion and mortality that exceeds 40% despite administration of antifungal therapy in modern intensive care unit facilities [1]. Hence, invasive candidiasis is an unmet medical condition for which better understanding of its pathogenesis at the host–pathogen interface is essential to improve patient outcomes. To that end, a mouse model of the infection, which introduces Candida yeast cells intravenously and mimics skin-derived bloodstream human candidiasis, has been successfully employed to study fungal and host factors that regulate susceptibility to the infection [2].

Highlights

Candida is the most common human fungal pathogen and the cause of invasive candidiasis, the fourth leading cause of nosocomial bloodstream infection in the United States with an estimated annual cost of,US$2 billion and mortality that exceeds 40% despite administration of antifungal therapy in modern intensive care unit facilities [1]
Studies in mice revealed that IFN-c and IL-17a produced by Th1 and Th17 lymphocytes were essential for vaccine-induced protection, via Ccl3- and Cxcl1-mediated neutrophil recruitment to sites of infection, which resulted in decreased Candida tissue burden [8]
A fundamental C. albicans virulence factor is its ability to transition between unicellular yeast cells and filamentous growth during infection; it is the interchange between these morphotypes that is critical for pathogenesis, as strains locked either in the yeast or the filamentous forms have attenuated virulence in vivo [9,10]

Summary

Introduction

Candida is the most common human fungal pathogen and the cause of invasive candidiasis, the fourth leading cause of nosocomial bloodstream infection in the United States with an estimated annual cost of ,US$2 billion and mortality that exceeds 40% despite administration of antifungal therapy in modern intensive care unit facilities [1]. Invasive candidiasis is an unmet medical condition for which better understanding of its pathogenesis at the host–pathogen interface is essential to improve patient outcomes. A mouse model of the infection, which introduces Candida yeast cells intravenously and mimics skin-derived bloodstream human candidiasis, has been successfully employed to study fungal and host factors that regulate susceptibility to the infection [2]

Which Candida Virulence Factors Influence the Outcome of Invasive Candidiasis?

How Does the Innate Immune System Recognize Candida?

What Are the Divergent Roles of Neutrophils during Invasive Candidiasis?

What Host Factors Mediate Protection against Invasive Candidiasis in Humans?