Lung eosinophil recruitment in response to Aspergillus fumigatus is correlated with fungal cell wall composition and requires γδ T cells

Abstract

The differential recognition of fungal cell wall polysaccharides that program innate and adaptive immunity to the human opportunistic fungal pathogen Aspergillus fumigatus has been a focus of considerable interest. In a mouse model of fungal conidia aspiration, decreased relative levels of cell wall core carbohydrates β-1,3-glucan to chitin in A. fumigatus isolates and mutant strains were correlated with increased airway eosinophil recruitment. In addition, an increase in fungal surface chitin exposure induced by the β-1,3-glucan synthesis-targeting drug caspofungin was associated with increased murine airway eosinophil recruitment after a single challenge of conidia. The response to increased A. fumigatus chitin was associated with increased transcription of IL-17A after a single aspiration, although this cytokine was not required for eosinophil recruitment. Rather, both RAG1 and γδ T cells were required, suggesting that this subset of innate-like lymphocytes may be an important regulator of potentially detrimental type 2 immune responses to fungal inhalation and infection.

Evolved to protect, designed to destroy: IL‐17‐producing γδ T cells in infection, inflammation, and cancer

“…In this regard, deficiency in IL-17 or γδ T cells did not reduce A. fumigatus burden in the lung of mice [42,43]. Instead, lack of γδ T cells appeared to confer protection from pulmonary aspergillosis [42,43]. Humans with lack of functional NADPH oxidase suffer from chronic granulomatous disease (CGD), which is characterized by recurrent bacterial and fungal infections, including Aspergillus, as well as uncontrolled inflammation [8].…”

“…In contrast to C. albicans , it appears that γδT17 cells are not required to protect against Aspergillus fumigatus . In this regard, deficiency in IL‐17 or γδ T cells did not reduce A. fumigatus burden in the lung of mice [42, 43]. Instead, lack of γδ T cells appeared to confer protection from pulmonary aspergillosis [42, 43].…”

Helper T‐cell responses and pulmonary fungal infections

“…Monocyte‐derived macrophages and dendritic cells are often recruited into the airway . Likewise, other myeloid cell populations, including neutrophils, monocytes and eosinophils, infiltrate the airways in an effort to combat the infection. In almost all cases of pulmonary fungal infection, the development of adaptive immunity and the engagement of CD4 T‐cell help is a key determinant of the outcome on infection.…”

The Fungal Microbiome and Asthma

“…Reese et al (2007) found chitin exposure in the airways to be associated with recruitment of IL-4-expressing innate immune cells, eosinophils, and basophils, along with an M2 macrophage phenotype in mice relative to a saline-challenged control ( Figure 3A). An increased chitin to bglucan expression ratio in A. fumigatus strains resulted in greater eosinophil recruitment in a mouse model of airway inflammation, dependent on gd-T cells, indicating the role of this T cell subset in the type 2 response to chitin (Amarsaikhan et al, 2017). Using Ccr1 -/mice, Blease et al (2000) showed that C-C Motif Chemokine Receptor 1 (CCR1) signalling is necessary for Th2 responses and airway remodeling in a A. fumigatus model of airway inflammation, another mechanism by which fungi are capable of eliciting such airway response.…”