Innate Immune Responses to Cryptococcus.

Lena Heung

doi:10.3390/jof3030035

Abstract

Cryptococcus species are encapsulated fungi found in the environment that predominantly cause disease in immunocompromised hosts after inhalation into the lungs. Even with contemporary antifungal regimens, patients with cryptococcosis continue to have high morbidity and mortality rates. The development of more effective therapies may depend on our understanding of the cellular and molecular mechanisms by which the host promotes sterilizing immunity against the fungus. This review will highlight our current knowledge of how Cryptococcus, primarily the species C. neoformans, is sensed by the mammalian host and how subsequent signaling pathways direct the anti-cryptococcal response by effector cells of the innate immune system.

Highlights

The encapsulated, yeast-like fungi of the genus Cryptococcus are prevalent throughout the environment worldwide
Despite modern-day combination antifungal therapy, the mortality rate for cryptococcal meningitis is estimated at 15–25% [4,5], and the at-risk population is expanding with the development of new immunosuppressive regimens for autoimmunity and cancer [6]
While the adaptive immune response to Cryptococcus is an important arm of anti-cryptococcal immunity, this review will focus on our current knowledge of innate immune responses to the species C. neoformans and identify significant questions that remain to be investigated

Summary

Introduction

The encapsulated, yeast-like fungi of the genus Cryptococcus are prevalent throughout the environment worldwide. The most common species that cause disease in humans are Cryptococcus neoformans and Cryptococcus gattii. These pathogens can cause a life-threatening meningoencephalitis after acquisition through the respiratory tract and subsequent dissemination to the central nervous system (CNS). While C. gattii can infect apparently immunocompetent hosts, C. neoformans is more often an opportunistic pathogen, affecting immunocompromised patients including those with HIV/AIDS, cancer and solid organ transplantation [1]. Cryptococcal meningitis has been estimated to affect up to 1 million people worldwide each year [2,3]. Despite modern-day combination antifungal therapy, the mortality rate for cryptococcal meningitis is estimated at 15–25% [4,5], and the at-risk population is expanding with the development of new immunosuppressive regimens for autoimmunity and cancer [6]. While the adaptive immune response to Cryptococcus is an important arm of anti-cryptococcal immunity (reviewed in [1,7,8]), this review will focus on our current knowledge of innate immune responses to the species C. neoformans and identify significant questions that remain to be investigated

Animal Models of Cryptococcosis

Host Recognition of Cryptococcus

C-Type Lectin Receptors

Toll-Like Receptors

Scavenger Receptors

Natural Antibodies

Complement and Other Soluble Mediators

Other Recognition Pathways

Intracellular Signaling Molecules

Effector Functions of Innate Immune Cells

Inflammatory Monocytes

Macrophages