Fungal-mediated lung allergic airway disease: The critical role of macrophages and dendritic cells

Abstract

Fungi are abundant in the environment, causing our lungs to be constantly exposed to a diverse range of species. While the majority of these are cleared effectively in healthy individuals, constant exposure to spores (especially Aspergillus spp.) can lead to the development of allergic inflammation that underpins and worsen diseases such as asthma. Despite this, the precise mechanisms that underpin the development of fungal allergic disease are poorly understood. Innate immune cells, such as macrophages (MΦs) and dendritic cells (DCs), have been shown to be critical for mediating allergic inflammation to a range of different allergens. This review will focus on the crucial role of MΦ and DCs in mediating antifungal immunity, evaluating how these immune cells mediate allergic inflammation within the context of the lung environment. Ultimately, we aim to highlight important future research questions that will lead to novel therapeutic strategies for fungal allergic diseases.

More than Just Protein Degradation: The Regulatory Roles and Moonlighting Functions of Extracellular Proteases Produced by Fungi Pathogenic for Humans

“…Representatives of the Aspergillus , Penicillium , Cladosporium , and Alternaria genera are the fungi that are most frequently identified as being involved in the development of inhalant allergy and asthma in humans [ 77 , 78 , 79 ]. The initial contact of an individual with a potentially allergenic substance of fungal origin is related to sensitization–interaction, and processing by dendritic cells and antigen presentation via the MHC Class II complex, followed by the induction of T helper 2 (Th2) lymphocytes in the presence of early interleukin 4 (IL-4), and subsequent immunoglobulin E (IgE) production by B lymphocytes [ 80 , 81 ].…”

A scoping review: What are the cellular mechanisms that drive the allergic inflammatory response to fungal allergens in the lung epithelium?

“…11 These disorders include asthma, chronic rhinosinusitis (CRS) and allergic bronchial pulmonary aspergillosis (ABPA), which affect millions of people globally. 1,[14][15][16][17] Typically, AAD is defined as an allergic response in individuals characterised by increased serum IgE, airway inflammation, airway remodelling (including peribronchial fibrosis and increased collagen deposition), increased type 2 cytokine profile (e.g. Interleukin (IL) 4, IL5, IL13, IL25, IL33, thymic stromal lymphopoietin (TSLP)), airway eosinophilia, mucus hypersecretion, and airway hyperresponsiveness (AHR).…”

“…Allergic airway disease (AAD) is a collective term for respiratory disorders that can be exacerbated upon exposure to airborne allergens, including fungal agents, pollen and house dust mite (HDM) 11 . These disorders include asthma, chronic rhinosinusitis (CRS) and allergic bronchial pulmonary aspergillosis (ABPA), which affect millions of people globally 1,14–17 …”

“…Fungi have specific features that are recognisable to the human immune system, termed pathogen‐associated molecular patterns (PAMPs) and include β‐glucan, chitin and mannans. In addition, fungi produce proteases and glycosidases to degrade material for nutrient release, which can also degrade epithelial tight junctions in the lung and induce allergic responses 1,4,11,13 …”

CARD9 balances Aspergillus fumigatus‐induced anti‐fungal immunity and allergic inflammation

“…As it possesses pathogenicity and allergenicity, A. fumigatus exposure can induce either Th1/Th17 dominated anti-fungal immunity or Th2 dominated allergic inflammation, or both based on the situations. 1,2 However, some investigations show that type-2 immunity can suppress Th1 mediated immune-protection against fungal infection, which promote fungal persistence and disease progression. 3 These data suggest that anti-fungal immunity and sensitization to fungal allergen are always in dynamic balance and overwhelming type-2 immune response may be detrimental for fungal elimination.…”