Factors Contributing to Sex Differences in Mice Inhaling Aspergillus fumigatus.

Andrea L Schaefer,Mai Ceesay,Jacob Tesch,Jennicca A Leier,Brian D Wisenden,Sumali Pandey

doi:10.3390/ijerph17238851

Andrea L Schaefer, Mai Ceesay + Show 4 more

Open Access

https://doi.org/10.3390/ijerph17238851

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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.

Highlights

While several federal agencies guide the public on health effects associated with environmental fungal exposure and on ways to mitigate it, there are no federally accepted health-based standards for safe fungal levels as reported by the United States Government Accountability Office (U.S GAO) [1]
We investigated the immune response of C57BL/6J mice to live, airborne A. fumigatus spores, and used sex and timepoint as predictor variables
We have previously shown that airway remodeling associates with increased granulocytic inflammation caused by repeated inhalation of live A. fumigatus spores [21]

Summary

Introduction

While several federal agencies guide the public on health effects associated with environmental fungal exposure and on ways to mitigate it, there are no federally accepted health-based standards for safe fungal levels as reported by the United States Government Accountability Office (U.S GAO) [1]. Diseases like cancer and farmer’s lung, have implicated mold-associated exposures [2,3,4]. Aspergillus fumigatus is one such environmental fungus, which is efficiently cleared from the lungs of an immunocompetent host, but can cause a variety of diseases in others, such as Severe Asthma with. The severity of infection/colonization can range from mortality associated with invasive aspergillosis, and ongoing morbidity associated with allergic conditions [5]. Exposure to this saprophytic fungus is ubiquitous in the environment, as it is commonly found in soil and air, and plays an important role in carbon and nitrogen recycling.

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