Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-12 (of 12 Records) |
Query Trace: Croston TL [original query] |
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Corrigendum: Persisting Cryptococcus yeast species Vishniacozyma victoriae and Cryptococcus neoformans elicit unique airway inflammation in mice following repeated exposure
Rush RE , Blackwood CB , Lemons AR , Dannemiller KC , Green BJ , Croston TL . Front Cell Infect Microbiol 2024 14 1381148 [This corrects the article DOI: 10.3389/fcimb.2023.1067475.]. |
Optimization of Aspergillus versicolor culture and aerosolization in a murine model of inhalational fungal exposure
Blackwood CB , Croston TL , Barnes MA , Lemons AR , Rush RE , Goldsmith T , McKinney WG , Anderson S , Weaver KL , Sulyok M , Park JH , Germolec D , Beezhold DH , Green B . J Fungi (Basel) 2023 9 (11) Aspergillus versicolor is ubiquitous in the environment and is particularly abundant in damp indoor spaces. Exposure to Aspergillus species, as well as other environmental fungi, has been linked to respiratory health outcomes, including asthma, allergy, and even local or disseminated infection. However, the pulmonary immunological mechanisms associated with repeated exposure to A. versicolor have remained relatively uncharacterized. Here, A. versicolor was cultured and desiccated on rice then placed in an acoustical generator system to achieve aerosolization. Mice were challenged with titrated doses of aerosolized conidia to examine deposition, lymphoproliferative properties, and immunotoxicological response to repeated inhalation exposures. The necessary dose to induce lymphoproliferation was identified, but not infection-like pathology. Further, it was determined that the dose was able to initiate localized immune responses. The data presented in this study demonstrate an optimized and reproducible method for delivering A. versicolor conidia to rodents via nose-only inhalation. Additionally, the feasibility of a long-term repeated exposure study was established. This experimental protocol can be used in future studies to investigate the physiological effects of repeated pulmonary exposure to fungal conidia utilizing a practical and relevant mode of delivery. In total, these data constitute an important foundation for subsequent research in the field. |
Persisting Cryptococcus yeastspecies Vishniacozyma victoriae and Cryptococcus neoformans elicit unique airway inflammation in mice following repeated exposure
Rush RE , Blackwood CB , Lemons AR , Green BJ , Croston TL . Front Cell Infect Microbiol 2023 13 1067475 BACKGROUND: Allergic airway disease (AAD) is a growing concern in industrialized nations and can be influenced by fungal exposures. Basidiomycota yeast species such as Cryptococcus neoformans are known to exacerbate allergic airway disease; however, recent indoor assessments have identified other Basidiomycota yeasts, including Vishniacozyma victoriae (syn. Cryptococcus victoriae), to be prevalent and potentially associated with asthma. Until now, the murine pulmonary immune response to repeated V. victoriae exposure was previously unexplored. OBJECTIVE: This study aimed to compare the immunological impact of repeated pulmonary exposure to Cryptococcus yeasts. METHODS: Mice were repeatedly exposed to an immunogenic dose of C. neoformans or V. victoriae via oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and lungs were collected to examine airway remodeling, inflammation, mucous production, cellular influx, and cytokine responses at 1 day and 21 days post final exposure. The responses to C. neoformans and V. victoriae were analyzed and compared. RESULTS: Following repeated exposure, both C. neoformans and V. victoriae cells were still detectable in the lungs 21 days post final exposure. Repeated C. neoformans exposure initiated myeloid and lymphoid cellular infiltration into the lung that worsened over time, as well as an IL-4 and IL-5 response compared to PBS-exposed controls. In contrast, repeated V. victoriae exposure induced a strong CD4(+) T cell-driven lymphoid response that started to resolve by 21 days post final exposure. DISCUSSION: C. neoformans remained in the lungs and exacerbated the pulmonary immune responses as expected following repeated exposure. The persistence of V. victoriae in the lung and strong lymphoid response following repeated exposure were unexpected given its lack of reported involvement in AAD. Given the abundance in indoor environments and industrial utilization of V. victoriae, these results highlight the importance to investigate the impact of frequently detected fungal organisms on the pulmonary response following inhalational exposure. Moreover, it is important to continue to address the knowledge gap involving Basidiomycota yeasts and their impact on AAD. |
Mycobiota and the contribution of yeasts in floor dust of 50 elementary schools characterized with sequencing internal transcribed spacer region of ribosomal DNA
Park JH , Lemons AR , Croston TL , Park Y , Roseman J , Green BJ , Cox-Ganser JM . Environ Sci Technol 2022 56 (16) 11493-11503 The assemblage of fungi including unicellular yeasts in schools is understudied. We conducted an environmental study to characterize fungal communities in classroom floor dust. We collected 500 samples from 50 elementary schools in Philadelphia, PA, and evaluated room dampness/mold conditions. Genomic DNA from dust was extracted for internal transcribed spacer 1 Illumina MiSeq sequencing to identify operational taxonomic units (OTUs) organized from DNA sequences. Differential abundance analyses were performed to examine significant differences in abundance among groups. We identified 724 genera from 1490 OTUs. The genus Epicoccum was not diverse but the most abundant (relative abundance = 18.9%). Fungi were less diverse but most dissimilar in composition in the most water-damaged classrooms compared to the least water-damaged, indicating differential effects of individual classroom water-damage on fungal compositions. We identified 62 yeast genera, representing 19.6% of DNA sequences. Cyberlindnera was the most abundant (6.1%), followed by Cryptococcus, Aureobasidium, Rhodotorula, and Candida. The average relative abundance of yeasts tended to increase with increasing dampness and mold score and was significantly (p-value = 0.048) higher in the most water-damaged classrooms (22.4%) than the least water-damaged classrooms (18.2%). Our study suggests the need for further research on the potential health effects associated with exposures to yeasts in schools. |
Aspergillus versicolor Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changes.
Ladd TB , Johnson JAJr , Mumaw CL , Greve HJ , Xuei X , Simpson E , Barnes MA , Green BJ , Croston TL , Ahmed C , Lemons A , Beezhold DH , Block ML . ASN Neuro 2021 13 17590914211019886 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 × 10(5) spores), or viable A. versicolor (3 × 10(5) 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. |
Vishniacozyma victoriae (syn. Cryptococcus victoriae) in the homes of asthmatic and non-asthmatic children in New York City
Rush RE , Dannemiller KC , Cochran SJ , Haines SR , Acosta L , Divjan A , Rundle AG , Miller RL , Perzanowski MS , Croston TL , Green BJ . J Expo Sci Environ Epidemiol 2021 32 (1) 48-59 BACKGROUND: Indoor environments contain a broad diversity of non-pathogenic Basidiomycota yeasts, but their role in exacerbating adverse health effects has remained unclear. OBJECTIVE: To understand the role of Vishniacozyma victoriae exposure and its impact on human health. METHODS: A qPCR assay was developed to detect and quantify an abundant indoor yeast species, Vishniacozyma victoriae (syn. Cryptococcus victoriae), from homes participating in the New York City Neighborhood Asthma and Allergy Study (NAAS). We evaluated the associations between V. victoriae, housing characteristics, and asthma relevant health endpoints. RESULTS: V. victoriae was quantified in 236 of the 256 bedroom floor dust samples ranging from less than 300-45,918 cell equivalents/mg of dust. Higher concentrations of V. victoriae were significantly associated with carpeted bedroom floors (P = 0.044), mean specific humidity (P = 0.004), winter (P < 0.0001) and spring (P = 0.001) seasons, and the presence of dog (P = 0.010) and dog allergen Can f 1 (P = 0.027). V. victoriae concentrations were lower in homes of children with asthma vs. without asthma (P = 0.027), an association observed only among the non-seroatopic children. |
Resolution of pulmonary inflammation induced by carbon nanotubes and fullerenes in mice: Role of macrophage polarization
Lim CS , Porter DW , Orandle MS , Green BJ , Barnes MA , Croston TL , Wolfarth MG , Battelli LA , Andrew ME , Beezhold DH , Siegel PD , Ma Q . Front Immunol 2020 11 1186 Pulmonary exposure to certain engineered nanomaterials (ENMs) causes chronic lesions like fibrosis and cancer in animal models as a result of unresolved inflammation. Resolution of inflammation involves the time-dependent biosynthesis of lipid mediators (LMs)-in particular, specialized pro-resolving mediators (SPMs). To understand how ENM-induced pulmonary inflammation is resolved, we analyzed the inflammatory and pro-resolving responses to fibrogenic multi-walled carbon nanotubes (MWCNTs, Mitsui-7) and low-toxicity fullerenes (fullerene C60, C60F). Pharyngeal aspiration of MWCNTs at 40 mug/mouse or C60F at a dose above 640 mug/mouse elicited pulmonary effects in B6C3F1 mice. Both ENMs stimulated acute inflammation, predominated by neutrophils, in the lung at day 1, which transitioned to histiocytic inflammation by day 7. By day 28, the lesion in MWCNT-exposed mice progressed to fibrotic granulomas, whereas it remained as alveolar histiocytosis in C60F-exposed mice. Flow cytometric profiling of whole lung lavage (WLL) cells revealed that neutrophil recruitment was the greatest at day 1 and declined to 36.6% of that level in MWCNT- and 16.8% in C60F-treated mice by day 7, and to basal levels by day 28, suggesting a rapid initiation phase and an extended resolution phase. Both ENMs induced high levels of proinflammatory leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) with peaks at day 1, and high levels of SPMs resolvin D1 (RvD1) and E1 (RvE1) with peaks at day 7. MWCNTs and C60F induced time-dependent polarization of M1 macrophages with a peak at day 1 and subsequently of M2 macrophages with a peak at day 7 in the lung, accompanied by elevated levels of type 1 or type 2 cytokines, respectively. M1 macrophages exhibited preferential induction of arachidonate 5-lipoxygenase activating protein (ALOX5AP), whereas M2 macrophages had a high level expression of arachidonate 15-lipoxygenase (ALOX15). Polarization of macrophages in vitro differentially induced ALOX5AP in M1 macrophages or ALOX15 in M2 macrophages resulting in increased preferential biosynthesis of proinflammatory LMs or SPMs. MWCNTs increased the M1- or M2-specific production of LMs accordingly. These findings support a mechanism by which persistent ENM-induced neutrophilic inflammation is actively resolved through time-dependent polarization of macrophages and enhanced biosynthesis of specialized LMs via distinct ALOX pathways. |
Cultivation and aerosolization of Stachybotrys chartarum for modeling pulmonary inhalation exposure
Lemons AR , Croston TL , Goldsmith WT , Barnes MA , Jaderson MA , Park JH , McKinney W , Beezhold DH , Green BJ . Inhal Toxicol 2019 31 1-11 Objective: Stachybotrys chartarum is a hydrophilic fungal species commonly found as a contaminant in water-damaged building materials. Although several studies have suggested that S. chartarum exposure elicits a variety of adverse health effects, the ability to characterize the pulmonary immune responses to exposure is limited by delivery methods that do not replicate environmental exposure. This study aimed to develop a method of S. chartarum aerosolization to better model inhalation exposures. Materials and methods: An acoustical generator system (AGS) was previously developed and utilized to aerosolize and deliver fungal spores to mice housed in a multi-animal nose-only exposure chamber. In this study, methods for cultivating, heat-inactivating, and aerosolizing two macrocyclic trichothecene-producing strains of S. chartartum using the AGS are described. Results and discussion: In addition to conidia, acoustical generation of one strain of S. chartarum resulted in the aerosolization of fungal fragments (<2 microm aerodynamic diameter) derived from conidia, phialides, and hyphae that initially comprised 50% of the total fungal particle count but was reduced to less than 10% over the duration of aerosolization. Acoustical generation of heat-inactivated S. chartarum did not result in a similar level of fragmentation. Delivery of dry, unextracted S. chartarum using these aerosolization methods resulted in pulmonary inflammation and immune cell infiltration in mice inhaling viable, but not heat-inactivated S. chartarum. Conclusions: These methods of S. chartarum growth and aerosolization allow for the delivery of fungal bioaerosols to rodents that may better simulate natural exposure within water-damaged indoor environments. |
Inhalation of Stachybotrys chartarum fragments induces pulmonary arterial remodeling
Croston TL , Lemons AR , Barnes MA , Goldsmith WT , Orandle MS , Nayak AP , Germolec DR , Green BJ , Beezhold DH . Am J Respir Cell Mol Biol 2019 62 (5) 563-576 Stachybotrys chartarum is a fungal contaminant within the built environment and a respiratory health concern in the United States. The objective of this study was to characterize the mechanisms influencing pulmonary immune responses to repeatedly inhaled S. chartarum. Groups of B6C3F1/N mice repeatedly inhaled viable trichothecene-producing S. chartarum conidia (Strain A or Strain B), heat-inactivated conidia, or HEPA-filtered air twice a week for 4 and 13 weeks. Strain A was found to produce higher amounts of respirable fragments compared to Strain B. Lung tissue, serum and bronchoalveolar lavage fluid (BALF) were collected at 24 and 48 hours following final exposure and processed for histology, flow cytometry, RNA, and proteomic analyses. At 4 weeks post-exposure, a Th2-mediated response was observed. After 13 weeks, a mixed T-cell response was observed following exposure to Strain A, compared to a Th2-mediated response following Strain B exposure. Following exposure, both strains induced pulmonary arterial remodeling at 13 weeks; however, Strain A-exposed mice progressed more quickly compared to Strain B-exposed mice. BALF was composed primarily of eosinophils, neutrophils, and macrophages. Both the immune response and the observed pulmonary arterial remodeling were supported by specific cellular, molecular, and proteomic profiles. The immunopathological responses occurred earlier in mice exposed to high fragment-producing Strain A. The rather striking induction of pulmonary remodeling by S. chartarum appears to be related to the presence of fungal fragments during exposure. |
Aspergillus fumigatus viability drives allergic responses to inhaled conidia
Nayak AP , Croston TL , Lemons AR , Goldsmith WT , Marshall NB , Kashon ML , Germolec DR , Beezhold DH , Green BJ . Ann Allergy Asthma Immunol 2018 121 (2) 200-210 e2 BACKGROUND: Aspergillus fumigatus induced allergic airway disease has been shown to involve conidial germination in vivo but the immunological mechanisms remain uncharacterized. OBJECTIVE: A subchronic murine exposure model was used to examine the immunological mediators that are regulated in response to either culturable or non-culturable A. fumigatus conidia. METHODS: Female B6C3F1/N mice were repeatedly dosed via inhalation with 1 x 105 viable or heat inactivated conidia (HIC), twice a week for 13 weeks (26 exposures). Control mice inhaled HEPA-filtered air. The influence of A. fumigatus conidial germination on the pulmonary immunopathological outcomes was evaluated by flow cytometry analysis of cellular infiltration in the airways, assessment of lung mRNA expression, and quantitative proteomics and histopathology of whole lung tissue. RESULTS: Repeated inhalation of viable conidia, but not HIC, resulted in allergic inflammation marked by vascular remodeling, extensive eosinophilia, and accumulation of alternatively activated macrophages (AAMs) in the murine airways. More specifically, mice that inhaled viable conidia resulted in a mixed TH1 and TH2 (IL-13) cytokine response. Recruitment of eosinophils corresponded with increased Ccl11 transcripts. Furthermore, genes associated with M2 or alternatively activated macrophage polarization (e.g. Arg1, Chil3 and Retnla) were significantly upregulated in viable A. fumigatus exposed mice. In mice inhaling HIC, CD4+ T cells expressing IFN-gamma (TH1) dominated the lymphocytic infiltration. Quantitative proteomics of the lung revealed metabolic reprogramming accompanied by mitochondrial dysfunction and endoplasmic reticulum stress stimulated by oxidative stress from repetitive microbial insult. CONCLUSION: Our studies demonstrate that A. fumigatus conidial viability in vivo is critical to the immunopathological presentation of chronic fungal allergic disease. |
MicroRNA regulation of host immune responses following fungal exposure
Croston TL , Lemons AR , Beezhold DH , Green BJ . Front Immunol 2018 9 170 Fungal bioaerosols are ubiquitous in the environment and human exposure can result in a variety of health effects ranging from systemic, subcutaneous, and cutaneous infections to respiratory morbidity including allergy, asthma, and hypersensitivity pneumonitis. Recent research has focused on the role of microRNAs (miRNAs) following fungal exposure and is overlooked, yet important, group of regulators capable of influencing fungal immune responses through a variety of cellular mechanisms. These small non-coding ribose nucleic acids function to regulate gene expression at the post-transcriptional level and have been shown to participate in multiple disease pathways including cancer, heart disease, apoptosis, as well as immune responses to microbial hazards and occupational allergens. Recent animal model studies have characterized miRNAs following the exposure to inflammatory stimuli. Studies focused on microbial exposure, including bacterial infections, as well as exposure to different allergens have shown miRNAs, such as miR-21, miR-146, miR-132, miR-155, and the let-7 family members, to be involved in immune and inflammatory responses. Interestingly, the few studies have assessed that the miRNA profiles following fungal exposure have identified the same critical miRNAs that have been characterized in other inflammatory-mediated and allergy-induced experimental models. Review of available in vitro, animal and human studies of exposures to Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Paracoccidioides brasiliensis, and Stachybotrys chartarum identified several miRNAs that were shared between responses to these species including miR-125 a/b (macrophage polarization/activation), miR-132 [toll-like receptor (TLR)2-mediated signaling], miR-146a (TLR mediated signaling, alternative macrophage activation), and miR-29a/b (natural killer cell function, C-leptin signaling, inhibition of Th1 immune response). Although these datasets provide preliminary insight into the role of miRNAs in fungal exposed models, interpretation of miRNA datasets can be challenging for researchers. To assist in navigating this rapidly evolving field, the aim of this review is to describe miRNAs in the framework of host recognition mechanisms and provide initial insight into the regulatory pathways in response to fungal exposure. |
Influence of Aspergillus fumigatus conidia viability on murine pulmonary microRNA and mRNA expression following subchronic inhalation exposure.
Croston TL , Nayak AP , Lemons AR , Goldsmith WT , Gu JK , Germolec DR , Beezhold DH , Green BJ . Clin Exp Allergy 2016 46 (10) 1315-27 BACKGROUND: Personal exposure to fungal bioaerosols derived from contaminated building materials or agricultural commodities may induce or exacerbate a variety of adverse health effects. The genomic mechanisms that underlie pulmonary immune responses to fungal bioaerosols have remained unclear. OBJECTIVE: The impact of fungal viability on the pulmonary microRNA and messenger RNA profiles that regulate murine immune responses was evaluated following subchronic inhalation exposure to Aspergillus fumigatus conidia. METHODS: Three groups of naive B6C3F1/N mice were exposed via nose-only inhalation to A. fumigatus viable conidia, heat-inactivated conidia, or HEPA-filtered air twice a week for 13 weeks. Total RNA was isolated from whole lung 24 and 48 hours post final exposure and was further processed for gene expression and microRNA array analysis. The molecular network pathways between viable and heat-inactivated conidia groups were evaluated. RESULTS: Comparison of datasets revealed increased Il4, Il13, and Il33 expression in mice exposed to viable versus heat-inactivated conidia. Of 415 microRNAs detected, approximately 50% were altered in mice exposed to viable versus heat-inactivated conidia 48 hours post exposure. Significantly downregulated (P < 0.05) miR-29a-3p was predicted to regulate TGF-beta3 and Clec7a, genes involved in innate responses to viable A. fumigatus. Also significantly downregulated (P < 0.05), miR-23b-3p regulates genes involved in pulmonary IL-13 and IL-33 responses and SMAD2, downstream of TGF-beta signaling. Using Ingenuity Pathway Analysis, a novel interaction was identified between viable conidia and SMAD2/3. CONCLUSION AND CLINICAL RELEVANCE: Examination of the pulmonary genetic profiles revealed differentially expressed genes and microRNAs following subchronic inhalation exposure to A. fumigatus. MicroRNAs regulating genes involved in the pulmonary immune responses were those with the greatest fold change. Specifically, germinating A. fumigatus conidia were associated with Clec7a and were predicted to interact with Il13 and Il33. Furthermore, altered microRNAs may serve as potential biomarkers to evaluate fungal exposure. |
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