A comparison between intratracheal and inhalation delivery of Aspergillus fumigatus conidia in the development of fungal allergic asthma in C57BL/6 mice

Abstract

SummaryAllergic asthma is a debilitating disease of the airways characterized by airway hyperresponsiveness, eosinophilic inflammation, goblet cell metaplasia with associated mucus hypersecretion, and airway wall remodelling events, particularly subepithelial fibrosis and smooth muscle cell hyperplasia. Animal models that accurately mimic these hallmarks of allergic airways disease are critical for studying mechanisms associated with the cellular and structural changes that lead to disease pathogenesis. Aspergillus fumigatus, is a common aeroallergen of human asthmatics. The intratracheal (IT) delivery of A. fumigatus conidia into the airways of sensitized mice has been described as a model of allergic disease. Here, we compared the IT model with a newly developed inhalation (IH) challenge model. The IH model allowed multiple fungal exposures, which resulted in an exacerbation to the allergic asthma phenotype. Increased recruitment of eosinophils and lymphocytes, the hallmark leukocytes of asthma, were noted with the IH model as compared to the IT model in which macrophages and neutrophils were more prominent. Immunoglobulin E (IgE) production was significantly greater after IH challenge, while that of IgG 2a was higher after IT challenge. Airway wall remodelling was pronounced in IHtreated mice, particularly after multiple allergen challenges. Although the IT model may be appropriate for the examination of the played by innate cells in the acute response to fungus, it fails to consistently reproduce the chronic remodelling hallmarks of allergic asthma. The ability of the IH challenge to mimic these characteristics recommends it as a model suited to study these important events.

Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus

“…Our previous data demonstrated that airway allergic inflammation subsides by 28 d after the second fungal inhalation and that architectural changes including fibrosis, smooth muscle cell hyperplasia, and hyaluronic acid deposition occurs in subepithelial regions of the airways (28)(29)(30). Mice in our model of CA+Flu comorbidity (with significantly fewer eosinophils) were susceptible to virus-induced morbidity marked by weight loss and lung epithelial damage, compared with AA+Flu group, which did not succumb to influenza (13).…”

Hyaluronan deposition and co-localization with inflammatory cells and collagen in a murine model of fungal allergic asthma

“…Many of the acute and chronic features of clinical fungal asthma are recapitulated in the experimental inhalation model of allergic asthma with Aspergillus sensitization that we have developed in our laboratory [4, 7, 9–12]. In particular, we observe increased eosinophilia, IgE production, and a robust ECM turn over, which is exaggerated upon subsequent challenges with conidia [9, 11]. However, the relationship between ECM accumulation and inflammatory cell recruitment has not been investigated in fungal allergic asthma.…”

Study of immunological aspects of aspergillosis in mice and effect of polyene macrolide antibiotic (SJA-95) and IFN-γ: A possible role of IFN-γ as an adjunct in antifungal therapy

“…Although, the intratracheal delivery may be appropriate for examination of the role played by the innate cells in the acute response to A. fumigatus, but there is an inconsistency to reproduce the chronic allergic asthma. However, inhalation challenge to mimic certain characteristic may be suited to study critical events [18]. All the same, the present methodology used in our experiments also present multiple exposures and also manifests well defined allergic disease or bronchopulmonary a common allergic human asthmatic.…”