Biology subjects

Garvey, S.

Publications and source records attributed to Garvey, S..

3 recordsLinked to original sources

bioRxiv2026

Development and translational validation of a novel mouse model for allergic rhinitis

Background: Approximately 30% of the North American population are affected by seasonal or perennial rhinitis. Allergens from cats are common triggers of allergic rhinitis. Importantly, cat allergic rhinitis (cat-AR) is a major risk factor for more severe allergic diseases, including asthma. Current therapies rarely achieve full symptom control and development of novel therapeutics is constrained by the lack of physiologically relevant preclinical models. Objective: Establishment of a clinically-informed mouse model of cat allergen exposure in humans. Methods: Controlled human exposure was performed using airborne natural cat dander (CD) in a validated environmental exposure facility. Nasal immune cells and IgE concentrations in serum and nasal samples were assessed. In mice, we established a 14-day intermittent intranasal sensitization and challenge protocol using the same CD allergens. Clinical signs in mice were objectively quantified using AI-based video detection. Cellular changes in the nose were assessed with level-specific, spatial resolution. Lastly, systemic sensitization was confirmed through serum IgE and intradermal ear challenge. Measurements and Main Results: Following CD exposure, cat-allergic participants displayed increased nasal symptoms and eosinophil influx. CD-sensitized mice recapitulated key clinical features, including increased nasal rubbing, elevated nasal immune cell infiltration, and systemic sensitization. Importantly, spatial investigation of the cellular changes revealed major changes in the turbinate and olfactory regions of the nose. Conclusions: This novel mouse model provides a translationally valuable platform for investigating local and systemic mechanisms of cat-AR. It will serve for mechanistic and therapeutic evaluations with the goal of improving clinical translation and therapeutic precision.

immunology↗

bioRxiv2023

Urbanization and fragmentation interact to drive mutualism breakdown and the rise of unstable pathogenic communities in forest soil

Temperate forests are particularly threatened by urbanization and fragmentation, with over 20% (120lJ000 km2) of recently urbanized land in the U.S. subsuming natural forests. We leveraged a unique, well-characterized urban-to-rural and forest edge-to-interior gradient to identify the combined impact of these two land use changes - urbanization and forest fragmentation - on soil microbial community in native, remnant forests. We found evidence of mutualism breakdown between trees and their fungal root mutualists (ectomycorrhizal (ECM) fungi) with urbanization, where ECM fungi colonized fewer tree roots and had less connectivity in soil microbiome networks in urban forests compared to rural forests. However, urbanization did not reduce the relative abundance of ECM fungi in forest soils; instead, forest fragmentation alone led to strong reductions in ECM fungal abundance. At forest edges, ECM fungi were replaced by plant and animal pathogens, as well as copiotrophic, xenobiotics-degrading, and nitrogen-cycling bacteria, including nitrifiers and denitrifiers. Urbanization and fragmentation interacted to generate "suites" of microbes, with urban interior forests harboring highly homogenized microbiomes, while edge forests microbiomes were more heterogeneous and less stable, showing increased vulnerability to low soil moisture. When scaled to the regional level, we found that forest soils are projected to harbor high abundances of fungal pathogens and denitrifying bacteria, even in rural areas, due to extreme, widespread forest fragmentation. Our results highlight the potential for soil microbiome dysfunction - including increased greenhouse gas production - in temperate forest regions that are subsumed by urban expansion, both now and in the future. Significance StatementUrbanization and forest fragmentation are increasingly altering Earths ecosystems, yet the effects on soil microbiomes, crucial for plant health and climate regulation, remain unclear. Our data indicate that, in forested land, these two combined, compounding stressors reshape the soil microbiome in ways that could lead to more pathogen infections of plants and animals, higher rates of N loss due to denitrification, and the possibility of tree symbiont extinctions. By identifying the specific environmental stressors that lead to these microbiome shifts, our analysis can be used to inform urban development and forest management plans to mitigate impacts on the soil microbiome to sustain environmental quality and the ecosystem services that remnant native forests provide to society in the coming decades. ClassificationBiological Sciences/Ecology

ecology↗

bioRxiv2021

Double stranded RNA drives innate immune responses, sickness behavior and cognitive impairment dependent on dsRNA length, IFNAR1 expression and age

Double stranded RNA is generated during viral replication. The synthetic analogue poly I:C is frequently used to mimic anti-viral innate immune responses in models of psychiatric and neurodegenerative disorders including schizophrenia, autism, Parkinsons disease and Alzheimers disease. Many studies perform limited analysis of innate immunity despite these responses potentially differing as a function of dsRNA molecular weight and age. Therefore fundamental questions relevant to impacts of systemic viral infection on brain function and integrity remain. Here, we studied innate immune-inducing properties of poly I:C preparations of different lengths and responses in adult and aged mice. High molecular weight (HMW) poly I:C (1-6kb, 12 mg/kg) produced more robust sickness behavior and more robust IL-6, IFN-I and TNF responses than poly I:C of <500 bases (low MW) preparations. This was partly overcome with higher doses of LMW (up to 80 mg/kg), but neither circulating IFN{beta} nor brain transcription of Irf7 were significantly induced by LMW poly I:C, despite brain Ifnb transcription, suggesting that brain IFN-dependent gene expression is predominantly triggered by circulating IFN{beta} binding of IFNAR1. In aged animals, poly I:C induced exaggerated IL-6, IL-1{beta} and IFN-I in the plasma and similar exaggerated brain cytokine responses. This was associated with acute working memory deficits selectively in aged mice. Thus, we demonstrate dsRNA length-, IFNAR1- and age-dependent effects on anti-viral inflammation and cognitive function. The data have implications for CNS symptoms of acute systemic viral infection such as those with SARS-CoV-2 and for models of maternal immune activation.

neuroscience↗