Lifelong human exposure to inhaled fungi and asymptomatic clearance is the norm

Epithelial, innate, and adaptive immune cell crosstalk underlies antifungal immunity

Fungi can exacerbate allergy through proteolytic action and cross-reactive T cells

Viruses and treatment of viral infections can impair antifungal immunity

The basis of pulmonary antifungal immunity informs vaccine approaches

The respiratory tree maintains sterilizing immunity against human fungal pathogens. Humans inhale ubiquitous filamentous molds and geographically restricted dimorphic fungal pathogens that form small airborne conidia. In addition, pathogenic yeasts, exemplified by encapsulated Cryptococcus species, and Pneumocystis pose significant fungal threats to the lung. Classically, fungal pneumonia occurs in immune compromised individuals, specifically in patients with HIV/AIDS, in patients with hematologic malignancies, in organ transplant recipients, and in patients treated with corticosteroids and targeted biologics that impair fungal immune surveillance in the lung. The emergence of fungal co-infections during severe influenza and COVID-19 underscores the impairment of fungus-specific host defense pathways in the lung by respiratory viruses and by medical therapies to treat viral infections. Beyond life-threatening invasive syndromes, fungal antigen exposure can exacerbate allergenic disease in the lung. In this review, we discuss emerging principles of lung-specific antifungal immunity, integrate the contributions and cooperation of lung epithelial, innate immune, and adaptive immune cells to mucosal barrier immunity, and highlight the pathogenesis of fungal-associated allergenic disease. Improved understanding of fungus-specific immunity in the respiratory tree has paved the way to develop improved diagnostic, pre-emptive, therapeutic, and vaccine approaches for fungal diseases of the lung.

Lung

Pneumonia

Infection

Fungus

Aspergillus

Cryptococcus

Histoplasma

Blastomyces

Talaromyces

Paracoccidioides

Mucorales

Mycosis

Mucomycosis

Immunity

Innate

Macrophage

Neutrophil

Monocyte

T cell

Lymphocyte

© 2023 Published by Elsevier Ltd.