A Fun-Guide to Innate Immune Responses to Fungal Infections

Abstract

Immunocompromised individuals are at high risk of developing severe fungal infections with high mortality rates, while fungal pathogens pose little risk to most healthy people. Poor therapeutic outcomes and growing antifungal resistance pose further challenges for treatments. Identifying specific immunomodulatory mechanisms exploited by fungal pathogens is critical for our understanding of fungal diseases and development of new therapies. A gap currently exists between the large body of literature concerning the innate immune response to fungal infections and the potential manipulation of host immune responses to aid clearance of infection. This review considers the innate immune mechanisms the host deploys to prevent fungal infection and how these mechanisms fail in immunocompromised hosts. Three clinically relevant fungal pathogens (Candida albicans, Cryptococcus spp. and Aspergillus spp.) will be explored. This review will also examine potential mechanisms of targeting the host therapeutically to improve outcomes of fungal infection.

Lung infections due to emerging fungal pathogens

“…A complex interplay between the host's immune system and the structural integrity of the lower airways and lung parenchyma determines whether the host can clear the inhaled particles or the inhalation leads to invasive disease [34 ▪▪ ,35 ▪ ]. In immunocompetent hosts, alveolar macrophages and neutrophils phagocytose and destroy the majority of conidia before they germinate, whereas T-cells neutralize molds or yeast that have succeeded in germinating before distant spread occurs [34 ▪▪ ,36 ▪▪ ]. In contrast, neutrophil and T-cell dysfunction facilitates fungal germination and spread [35 ▪ ].…”

Human–Fungal Pathogen Interactions from the Perspective of Immunoproteomics Analyses

“…The adaptive immune system, in response to fungal invasion, has two major arms: (i) cellular-mediated immunity (CMI) and (ii) humoral-mediated immunity (HMI or antibody-mediated immunity). Several topics related to fungal immunity, such as cellular recognition [ 12 , 13 ], innate immunity [ 14 , 15 ], adaptive immunity [ 16 , 17 ], and predisposed genetic factors leading to fungal infections [ 18 ], have been analyzed in other outstanding reviews. In this review section, the humoral responses mediated by B-cells and antibodies are mainly discussed to emphasize the significance of identified antigenic proteins from pathogenic fungi.…”

Recent developments in membrane targeting antifungal agents to mitigate antifungal resistance

“…4 Cells of innate response like neutrophils and dendritic cells can cause direct antifungal effects or can secrete microbicidal compounds to clear fungal infections. [5][6][7] Notably, the host immune system acts as a defence army against fungal infections. However, immunocompromised patients are always at high risk as employment of immunosuppressive drugs in clinical settings and advent of HIV patients are important factors for increased number of immunocompromised individuals.…”