Publications by authors named "Sloan A Lewis"

Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting booster responses and generate experimental data for the explicit purpose of model evaluation.

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Background: Alcohol consumption is widespread with over half of the individuals over 18 years of age in the U.S. reporting alcohol use in the last 30 days.

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Article Synopsis
  • Chronic infections and cancers cause T cell exhaustion, leading to challenges in the immune response against these conditions.
  • The study identifies HMGB2 as a critical protein that supports the differentiation and maintenance of exhausted CD8 T cells, specifically stem-like progenitor T cells (Tpex) during persistent viral infections and tumors.
  • HMGB2's role suggests it could be a potential target for future T cell-based immunotherapies, highlighting its importance in improving immune responses.
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Chronic heavy alcohol drinking (CHD) rewires monocytes and macrophages toward heightened inflammatory states with compromised antimicrobial defenses that persist after 1-month abstinence. To determine whether these changes are mediated through alterations in the bone marrow niche, we profiled monocytes and hematopoietic stem cell progenitors (HSCPs) from CHD rhesus macaques using a combination of functional assays and single cell genomics. CHD resulted in transcriptional profiles consistent with increased activation and inflammation within bone marrow resident monocytes and macrophages.

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  • Cow milk (CM) allergy is a common issue in young children, but current diagnostic methods are often unreliable or risky.
  • This study aimed to identify specific characteristics of T cells in CM-allergic patients that could serve as a new diagnostic marker.
  • The researchers found significant differences in the quantity and behavior of CM-specific T cells in allergic patients, leading to the development of a flow-cytometry assay that could help with diagnosing CM allergy more effectively.
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Alcohol consumption is widespread with over half of the individuals over 18 years of age in the U.S. reporting alcohol use in the last 30 days.

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Chronic alcohol drinking rewires circulating monocytes and tissue-resident macrophages towards heightened inflammatory states with compromised anti-microbial defenses. As these effects remain consistent in short-lived monocytes after a 1-month abstinence period it is unclear whether these changes are restricted to the periphery or mediated through alterations in the progenitor niche. To test this hypothesis, we profiled monocytes/macrophages and hematopoietic stem cell progenitors (HSCP) of the bone marrow compartment from rhesus macaques after 12 months of ethanol consumption using a combination of functional assays and single cell genomics.

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Article Synopsis
  • - Alcohol misuse disrupts immune responses and causes dysfunction in multiple organs, leading to increased health risks for individuals with alcohol use disorders.
  • - Key immune cells in the brain, lungs, and liver are essential for maintaining immune defense and tissue health, but their effectiveness is reduced by binge drinking and chronic alcohol use.
  • - The review discusses recent findings on how alcohol misuse negatively impacts immune function and suggests areas for further research to better understand these effects, especially in relation to aging and gut health.
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  • T cells are believed to play a significant role in food allergies, but there's limited understanding of how they contribute to the allergic response and what specific markers identify these T cells.
  • Recent advancements in technology allow researchers to isolate and study these rare, antigen-specific T cells at a single-cell level, although food allergens still have fewer identified epitopes compared to infectious diseases.
  • By mapping T-cell phenotypes in food allergies and comparing them to other allergic and infectious diseases, researchers hope to establish a better understanding of pathologic T cells, which could lead to more efficient diagnostic methods and novel treatment targets.
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Aging is associated with increased monocyte production and altered monocyte function. Classical monocytes are heterogenous and a shift in their subset composition may underlie some of their apparent functional changes during aging. We have previously shown that mouse granulocyte-monocyte progenitors (GMPs) produce "neutrophil-like" monocytes (NeuMo), whereas monocyte-dendritic cell progenitors (MDPs) produce monocyte-derived dendritic cell (moDC)-producing monocytes (DCMo).

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Older individuals are at increased risk of developing severe respiratory infections. However, our understanding of the impact of aging on the respiratory tract remains limited as samples from healthy humans are challenging to obtain and results can be confounded by variables such as smoking and diet. Here, we carry out a comprehensive cross-sectional study (n = 34 adult, n = 49 aged) to define the consequences of aging on the lung using the rhesus macaque model.

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Chronic alcohol drinking is associated with increased susceptibility to viral and bacterial respiratory pathogens. In this study, we use a rhesus macaque model of voluntary ethanol self-administration to study the effects of long-term alcohol drinking on the immunological landscape of the lung. We report a heightened inflammatory state in alveolar macrophages (AMs) obtained from ethanol (EtOH)-drinking animals that is accompanied by increased chromatin accessibility in intergenic regions that regulate inflammatory genes and contain binding motifs for transcription factors AP-1, IRF8, and NFKB p-65.

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mRNA vaccines for SARS-CoV-2 have shown exceptional clinical efficacy, providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used scRNA-Seq and functional assays to compare humoral and cellular responses to 2 doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease.

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Background: Long-term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNAs (EV-miRNAs) have been found to be consistent biomarkers of conditions that include cancer and liver disease.

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In this study, peripheral blood mononuclear cells from young and old patients with COVID-19 were examined phenotypically, transcriptionally and functionally to reveal age-, time- and severity-specific adaptations. Gene signatures within memory B cells and plasmablasts correlated with reduced frequency of antigen-specific B cells and neutralizing antibodies in older patients with severe COVID-19. Moreover, these patients exhibited exacerbated T cell lymphopenia, which correlated with lower plasma interleukin-2, and diminished antigen-specific T cell responses.

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Chronic heavy drinking (CHD) of alcohol is a known risk factor for increased susceptibility to bacterial and viral infection as well as impaired wound healing. Evidence suggests that these defects are mediated by a dysregulated inflammatory response originating from myeloid cells, notably monocytes and macrophages, but the mechanisms remain poorly understood. Our ability to study CHD is impacted by the complexities of human drinking patterns and behavior as well as comorbidities and confounding risk factors for patients with alcohol use disorders.

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Article Synopsis
  • * A study examined the effects of chronic drinking on lamina propria leukocytes (LPLs) from different gut regions, revealing no significant resting state differences but notable functional distinctions in response to stimulation.
  • * The research indicates that alcohol impacts LPL responses in specific gut regions, with duodenal LPLs showing a reduced response and both ileal and jejunal LPLs exhibiting heightened activity, highlighting the complexity of alcohol-related intestinal damage.
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