Novel Mouse Models of Fungal Asthma

Alternaria alternata is a ubiquitous fungus and a major allergen associated with the development of asthma. Inhalation of intact spores is the primary cause of human exposure to fungal allergen. However, allergen-rich cultured fungal filtrates are oftentimes used in the current models of fungal sensitization that do not fully reflect real-life exposures. Thus, establishing novel spore exposure models is imperative. In this study, we established novel fungal exposure models of both adult and neonate to live spores. We examined pathophysiological changes in the spore models as compared to the non-exposure controls and also to the conventional filtrate models. While both Alternaria filtrate- and spore-exposed adult BALB/c mice developed elevated airway hyperresponsiveness (AHR), filtrates induced a greater IgE mediated response and higher broncholavage eosinophils than spores. In contrast, the mice exposed to Alternaria spores had higher numbers of neutrophils. Both exposures induced comparable levels of lung tissue inflammation and mucous cell metaplasia (MCM). In the neonatal model, exposure to Alternaria spores resulted in a significant increase of AHR in both adult and neonatal mice. Increased levels of IgE in both neonatal and adult mice exposed to spores was associated with increased eosinophilia in the treatment groups. Adult demonstrated increased numbers of lymphocytes that was paralleled by increased IgG1 production. Both adults and neonates demonstrated similarly increased eosinophilia, IgE, tissue inflammation and MCM.

Fungal Lung: The Risk of Fungal Exposure to Nail Care Professionals

Foot and nail care specialists spend a great portion of their day using nail drills to reduce nail thickness and smooth foot callouses. This process generates a large amount of dust, some of which is small enough to breathe in and deposit into the deepest regions of the respiratory tract, potentially causing health problems. Foot and nail dust often contain fungi, from both fungally-infected and healthy-looking nails. While the majority of healthy individuals can tolerate inhaled fungi, the immune systems of older, immunocompromised, and allergy-prone individuals often react using the inflammatory TH2 pathway, leading to mucus overproduction, bronchoconstriction, and, in severe cases, lung tissue damage. To protect vulnerable podiatry professionals, wearing a surgical mask, using a water spray suppression system on nail drills, installing air filtration systems, and considering drilling technique can help reduce the exposure to nail dust.

Presence of Pathogen-killed Larvae Influences Nesting Behavior of the Alfalfa Leafcutting Bee (Hymenoptera: Megachilidae)

The alfalfa leafcutting bee (Megachile rotundata (Fabricius)), a commercial pollinator used for alfalfa seed production, is susceptible to chalkbrood disease via ingested fungal spores. Diseases of insects can elicit behavioral changes in their hosts, but there are no recorded behaviors of alfalfa leafcutting bees in response to this fungal exposure. We conducted field studies to determine whether bees in pathogen-dense environments altered their nesting patterns, specifically if bees exposed to fungal spores produced higher numbers of nest cells and whether the proportions of nest cells that failed as eggs or small larvae (a state known as ‘pollen ball’) were greater. We found that our control bees, nontreated bees which were not exposed to chalkbrood spores other than those in the natural environment, had the highest proportion of pollen ball cells. Bees experimentally exposed to infective spores created the lowest number of nests and the fewest cells. Bees experimentally exposed to heat killed noninfective spores produced the greatest number of nests and cells overall and the greatest number of healthy progeny. We conclude that there are underlying behaviors that are elicited in response to the presence of chalkbrood spores that reduce the proportion of failed nest cells (grooming) and increase retention of bees at nesting sites (delay of bee emergence). Through further study of these behaviors, bee managers can potentially increase the productivity of their bee populations.

Aspergillus versicolor Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changes

Increasing evidence associates indoor fungal exposure with deleterious central nervous system (CNS) health, such as cognitive and emotional deficits in children and adults, but the specific mechanisms by which it might impact the brain are poorly understood. Mice were exposed to filtered air, heat-inactivated Aspergillus versicolor (3 × 105 spores), or viable A. versicolor (3 × 105 spores) via nose-only inhalation exposure 2 times per week for 1, 2, or 4 weeks. Analysis of cortex, midbrain, olfactory bulb, and cerebellum tissue from mice exposed to viable A. versicolor spores for 1, 2, and 4 weeks revealed significantly elevated pro-inflammatory ( Tnf and Il1b) and glial activity ( Gdnf and Cxc3r1) gene expression in several brain regions when compared to filtered air control, with the most consistent and pronounced neuroimmune response 48H following the 4-week exposure in the midbrain and frontal lobe. Bulk RNA-seq analysis of the midbrain tissue confirmed that 4 weeks of A. versicolor exposure resulted in significant transcriptional enrichment of several biological pathways compared to the filtered air control, including neuroinflammation, glial cell activation, and regulation of postsynaptic organization. Upregulation of Drd1, Penk, and Pdyn mRNA expression was confirmed in the 4-week A. versicolor exposed midbrain tissue, highlighting that gene expression important for neurotransmission was affected by repeated A. versicolor inhalation exposure. Taken together, these findings indicate that the brain can detect and respond to A. versicolor inhalation exposure with changes in neuroimmune and neurotransmission gene expression, providing much needed insight into how inhaled fungal exposures can affect CNS responses and regulate neuroimmune homeostasis.

Does a mobile dust-containment cart reduce the risk of healthcare-associated fungal infections during above-ceiling work?

Immunocompromised patients are at risk for infections due to above-ceiling activities in hospitals. Mobile dust-containment carts are available as environmental controls, but no published data support their efficacy. Using microbial air sampling and particle counts, we provide evidence of reduced risk of fungal exposure during open ceiling activities.

The Role of Home Fungal Exposure in Allergic Fungal Rhinosinusitis

Background Allergic fungal rhinosinusitis (AFRS) is disproportionately identified in patients of low socioeconomic status living in warm, humid climates, and is thought to occur in response to environmental fungal species. Objective We hypothesized that micro-geographic differences in fungal exposure contribute to the pathogenesis of AFRS, and compared home fungal exposure of patients with AFRS to normative data and controls. Methods Comprehensive prospective enrollment and data capture was completed in 70 patients. Patients with AFRS were compared to a control population with chronic rhinosinusitis with nasal polyposis (CRSwNP) and comorbid atopy. Comprehensive demographics, 22-item sino-nasal outcomes test (SNOT-22) questionnaires, and endoscopy scores were compiled. Using a test strip collection system, a home fungal assessment was completed for each patient, along with detailed questions related to home condition. Results Patients with AFRS were more likely to be younger (p<.001), African American (p<.001), from a lower income bracket (p < .012), and less likely to own their home (p < .001). There were no differences in prior surgeries (p=.432), endoscopy scores (p = .409) or SNOT-22 scores (p = .110) between the groups. There were no differences in overall fungal counts between patients with AFRS and controls (p = .981). AFRS patients had a higher prevalence of Basidiospores than controls (p = .034). Conclusion This study failed to detect differences in total home fungal exposure levels between those with AFRS and atopic CRSwNP, despite differences in socioeconomic status. This suggests that absolute fungal levels may not be the primary driver in development of AFRS, or that the fungal detection strategies utilized were not representative of patients’ overall fungal exposure.