Investigation of inflammatory and allergic responses to common mold species: Results from in vitro experiments, from a mouse model of asthma, and from a group of asthmatic patients

Abstract

Most studies on molds focus on Alternaria alternata and Aspergillus fumigatus. Here, we report on inflammatory and allergenic properties of more typical indoor species Aspergillus versicolor, P. chrysogenum, C. cladosporioïdes, and C. sphaerospermum that were compared to A. alternata and A. fumigatus. In a mouse model, after intranasal instillation, A. alternaria, A. versicolor, and C. sphaerospermum induced the early recruitment of neutrophils and the strong expression of inflammatory markers in the bronchoalveolar lavages fluids. A. fumigatus also induced the early accumulation of neutrophils but with lower levels of inflammatory markers. Chronic treatment induced variable response according to species: P. chrysogenum and A. fumigatus appeared strong pro-allergenic inducers compared to A. alternata and C. sphaerospermum while A. versicolor and C. cladosporioides induced a mixed pro-allergenic/pro-inflammatory response. In mold-sensitized asthmatics, mold-specific Immunoglobulin E (IgE) were detected with an in-house dot-blot assay. A. fumigatus and A. alternata were the most frequent sensitizers. Altogether, P. chrysogenum, P. brevicompactum, C. sphaerospermum, and C. cladosporïoides were the "major sensitizer" (defined as the strongest response against a single mold species) for almost 30% of the asthmatics. These results show that, not only A. alternata and A. fumigatus, but also indoor species have strong inflammatory and allergic properties and a harmful potency.

Characterization and pro‐inflammatory potential of indoor mold particles

“…Previous studies have reported similar differences between the two Aspergillus spp. in mouse dendritic cells . In accordance, no production of inflammatory mediators was induced by A versicolor in mouse RAW264.7, human 28SC macrophages, or A549 lung epithelial cell lines …”

“…Chronic inflammation is often found to be a key factor in mold-induced pulmonary diseases (Figure 1). There is a positive association between mold exposure and elevated levels of pro-inflammatory markers in the airways, [102][103][104] which are linked to several respiratory diseases.…”

Fungal aerosol composition in moldy basements

“…Morphological diversity of fungal particles (spherical, oblong, or fiber‐like in shape) may influence the particles aerodynamic deposition patterns in the human respiratory tract upon inhalation, and the type of immune reactions induced through cytokines, chemokines from involved immune cells dependent on the deposition sites in the airways . Species diversity is also of great importance as some common indoor fungi induce particularly allergenic responses versus others that induce non‐allergic inflammatory reactions . Therefore, we may get new insights in the role played by fungi in respiratory morbidity when we base our characterization on a holistic approach.…”

Pro-Inflammatory Responses in Human Bronchial Epithelial Cells Induced by Spores and Hyphal Fragments of Common Damp Indoor Molds

“…When inhaled, they may germinate and form hyphae [10]. While A. fumigatus is pathogenic [11,12,13], P. chrysogenum is rarely responsible for invasive disease [14,15].…”

“…However, the impact of various mold species with regard to respiratory diseases associated with inflammatory effects has not been fully elucidated. Notably, the relative levels of A. fumigatus in indoor air are low compared to P. chrysogenum [24] which is highly predominant in indoor air [14,15]. Pro-inflammatory responses are central key elements for reducing the chances of infection due to exposure to bacteria as well as mold [10].…”