Biology subjects

Tuttle, E.

Publications and source records attributed to Tuttle, E..

3 recordsLinked to original sources

bioRxiv2025

Distinct phenotypes and repertoires of bronchoalveolar and airway mucosal T cells in health and allergic asthma

BackgroundT cells play a central role in host protection against respiratory pathogens, but a maladaptive T cell response can lead to pulmonary diseases. Defining the biology of protective versus pathogenic T cell responses in the lungs of humans will be critical to nominate novel approaches to improve respiratory health. Previous studies have examined T cells from the lungs captured via bronchoalveolar lavage (BAL), endobronchial brushings, or biopsies. However, whether these different approaches are capturing distinct T cell phenotypes and/or clonotypes remains unclear. ObjectiveTo evaluate and compare the transcriptional signatures of T cells isolated via BAL versus endobronchial brushings in healthy controls (HCs) and allergic asthmatics (AAs). MethodsFlexible bronchoscopy was performed to obtain BAL and endobronchial brushings from 3 HC and 3 AA subjects. CD3+ T cells were sorted and single cell RNA- and T cell receptor (TCR)-sequencing was performed using the 10X Chromium platform. Unbiased clustering, differential gene expression analysis and TCR repertoire analysis was performed. ResultsUnbiased clustering analysis allowed us to define 7 CD8 and 6 CD4 T cell subsets. The most significant difference in T cell subsets abundance between AAs and HCs was the enrichment of CD4 T helper type 2 (Th2) cells when comparing endobronchial brush samples (OR=26.2, P=0.002), but not when examining BAL (OR=1.7, P=0.46), indicating differences in the T cell subsets captured from the BAL versus airway mucosa specimen processing. In further support of this observation, comparing the BAL and brush T cells across all subjects revealed an up-regulation of resident-memory T cell markers (i.e. ITGAE, CD69) in brush T cells versus BAL T cells in both CD4 and CD8 lineages. In contrast, BAL CD8 and CD4 T cells exhibited an enriched type I and II interferon signatures compared to brush T cells. Lastly, TCR repertoire analysis revealed that brush T cells contained dramatically expanded TCR clones. Expanded T cell clones from the brush expressed high levels of resident-memory markers, suggesting the airway mucosa is enriched for TRM cells with unique TCR specificity. ConclusionsSampling T cells via BAL versus airway brushings yielded distinct T cell phenotypes and clonotypes with important implications for future research in lung immunology.

immunology↗

bioRxiv2023

Comammox bacterial preference for urea influences its interactions with aerobic nitrifiers.

While the co-existence of comammox bacteria with canonical nitrifiers is well documented in diverse ecosystems, there is still a dearth of knowledge about the mechanisms underpinning their interactions. Understanding these interaction mechanisms is important as they may play a critical role in governing nitrogen biotransformation in natural and engineered ecosystems. In this study, we tested the ability of two environmentally relevant factors (nitrogen source and availability) to shape interactions between strict ammonia and nitrite-oxidizing bacteria and comammox bacteria in continuous flow column reactors. The composition of inorganic nitrogen species in reactors fed either ammonia or urea was similar during the lowest nitrogen loading condition (1 mg-N/L), but higher loadings (2 and 4 mg-N/L) promoted significant differences in nitrogen species composition and nitrifier abundances. The abundance and diversity of comammox bacteria were dependent on both nitrogen source and loading conditions as multiple comammox bacterial populations were preferentially enriched in the urea-fed system. In contrast, their abundance was reduced in response to higher nitrogen loadings in the ammonia-fed system likely due to ammonia-based inhibition. The preferential enrichment of comammox bacteria in the urea-fed system could be associated with their ureolytic activity calibrated to their ammonia oxidation rates thus minimizing ammonia accumulation to inhibitory levels. However, an increased abundance of comammox bacteria was not associated with a reduced abundance of nitrite oxidizers in the urea-fed system while a negative correlation was found between them in the ammonia-fed system; the latter dynamic likely emerging from reduced availability of nitrite to strict nitrite oxidizers at low ammonia loading conditions. ImportanceNitrification is an essential biological process in drinking water and wastewater treatment systems for managing nitrogen and protecting downstream water quality. The discovery of comammox bacteria and their detection alongside canonical nitrifiers in these engineered ecosystems has made it necessary to understand the environmental conditions that regulate their abundance and activity relative to other better-studied nitrifiers. This study aimed to evaluate two important factors that could potentially influence the behavior of nitrifying bacteria, and therefore impact nitrification processes. Colum reactors fed with either ammonia or urea were systematically monitored to capture changes in nitrogen biotransformation and the nitrifying community as a function of influent nitrogen concentration, nitrogen source, and reactor depth. Our findings show that comammox bacterial abundance decreased and that of nitrite oxidizers increased with increased ammonia availability, while their abundance and diversity increased with increasing urea availability without driving a reduction in the abundance of canonical nitrifiers.

microbiology↗

bioRxiv2018

Parent and offspring genotypes influence gene expression in early life

Parents can have profound effects on offspring fitness. Little, however, is known about the mechanisms through which parental care variation influences offspring physiology in natural systems. White-throated sparrows Zonotrichia albicollis (WTSPs) exist in two genetic morphs, tan and white, controlled by a large polymorphic supergene. Morphs mate disassortatively, resulting in two pair types: tan male x white female (TxW) pairs, which provide biparental care and white male x tan female (WxT) pairs, which provide female-biased care. To investigate the effects of parental care variation, we performed RNA-seq on WTSP nestlings sampled from nests of both pair types. Pair type had the largest effect on nestling gene expression, with 881 genes differentially expressed (DE) and seven correlated gene co-expression modules. The DE genes and modules up-regulated in nests with female-biased parental care primarily function in metabolism and stress-related pathways resulting from the overrepresentation of stress response and proteolysis genes. These results show that parental genotypes, a proxy for parental care in this system, alter nestling physiology and highlight avenues of further research investigating the ultimate implications of alternative parental care strategies. Nestlings also exhibited morph-specific gene expression, driven by innate immunity genes and co-expression of genes located in the supergene. Remarkably, we identified the same regulatory hub genes in these blood-derived expression networks as were previously identified in WTSP brains (EPM2A, BPNT1, TAF5L). These hub genes were located within the supergene, highlighting the importance of this gene complex in structuring regulatory networks across diverse tissues.

genomics↗