Factors Contributing to Sex Differences in Mice Inhaling Aspergillus fumigatus

Abstract

Aspergillus fumigatus is a respiratory fungal pathogen and an allergen, commonly detected in flooded indoor environments and agricultural settings. Previous studies in Balb/c mice showed that repeated inhalation of live and dry A. fumigatus spores, without any adjuvant, elevated allergic immune response and airway remodeling. Sex-specific differences can influence host-pathogen interactions and allergic-asthma related outcomes. However, the effect of host sex on immune response, in the context of A. fumigatus exposure, remains unknown. In this study, we quantified the multivariate and univariate immune response of C57BL/6J mice to live, dry airborne A. fumigatus spores. Our results corroborate previous results in Balb/c mice that repeated inhalation of live A. fumigatus spores is sufficient to induce mucus production and inflammation by day 3 post last challenge, and antibody titers and collagen production by day 28 post-challenge. Principal Component Analysis (PCA) showed that females exhibited significantly higher levels of immune components than males did. Taken together, our data indicate that host-sex is an important factor in shaping the immune response against A. fumigatus, and must be considered when modeling disease in animals, in designing diagnostics and therapeutics for A. fumigatus-associated diseases or while drafting evidence-based guidelines for safe mold levels.

Let's talk about sex characteristics—As a risk factor for invasive fungal diseases

“…Steroid hormones and sex‐specific immune responses lead to different host‐pathogen interactions in Aspergillus infections ( Figure 3 ). 40 Until recently, these sex‐specific distinctions in animals exposed to Aspergillus remained unknown. Schaefer et al showed that female mice generally exhibit higher immune responses, including antibody titres and granulocyte and lymphocyte recruitment than male mice 40 .…”

“… 40 Until recently, these sex‐specific distinctions in animals exposed to Aspergillus remained unknown. Schaefer et al showed that female mice generally exhibit higher immune responses, including antibody titres and granulocyte and lymphocyte recruitment than male mice 40 . To date, sex differences are still rarely reported in animal models studying Aspergillus infections 39 .…”

“…In vitro/animal models are fundamental in Aspergillus infections (Figure 3). 40 Until recently, these sex-specific distinctions in animals exposed to Aspergillus remained unknown.…”

“…Schaefer et al showed that female mice generally exhibit higher immune responses, including antibody titres and granulocyte and lymphocyte recruitment than male mice. 40 To date, sex differences are still rarely reported in animal models studying Aspergillus infections. 39 In order to generate reliable and reproducible data, sex needs to be addressed in future studies as an important step towards standardised protocols.…”

Epidermal Club Cells in Fishes: A Case for Ecoimmunological Analysis

“…Another important, yet under-investigated area is the interaction between sex hormones and ECCs and immune function. In mice and humans, sex hormones can affect the immune response to pathogens [ 175 , 176 , 177 ]. Testosterone is known to affect the immune system in fish [ 178 , 179 , 180 , 181 ].…”