Biology subjects

Messaoudi, I.

Publications and source records attributed to Messaoudi, I..

At least 19 recordsLinked to original sources

bioRxiv2026

Spontaneous Pregravid Obesity Reshapes Fetal Immune Ontogeny in a Nonhuman Primate Model

Pregravid obesity is associated with longterm immune alterations in the offspring; however, the mechanisms remain poorly defined. To address this gap, we investigated the impact of spontaneous pregravid obesity, independent of obesogenic diet, on fetal immune ontogeny in a rhesus macaque model. Using spectral flow cytometry, multiplex cytokine profiling, functional stimulation assays, and singlecell RNA sequencing, we profiled immune composition, function, transcriptional profiles, and intercellular communication in umbilical cord blood as well as fetal spleen and lung. Pregravid obesity was associated with altered fetal organ growth, elevated inflammatory mediators, altered frequencies of immune cell populations, and hyperresponsiveness to stimulation by splenic and lung leukocytes. Singlecell transcriptomic analyses revealed tissuespecific reprogramming of innate immune cells, including heightened inflammatory, migratory, and metabolic signatures with impaired antigen presentation. Moreover, there was evidence of impaired T cell differentiation, premature effector differentiation, and B cell dysfunction. Cell-cell communication analysis identified loss of tolerogenic signaling and enhanced proinflammatory pathways across spleen and lung myeloid cells. These findings demonstrate that spontaneous pregravid obesity fundamentally reshapes fetal circulating and tissueresident immune cells, providing mechanistic insight into the increased susceptibility to infection, respiratory diseases, and immune dysregulation observed in offspring of mothers with obesity.

immunology↗

bioRxiv2026

Maternal Obesity Reprograms Differentiation Trajectories of Fetal Hematopoietic Stem and Progenitor Cells Through Altered Inflammatory Signaling

BackgroundMaternal obesity is a global health challenge with profound consequences for offspring health. While its impact on metabolic programming has been widely studied, far less is known about how maternal obesity shapes the fetal immune system. The fetal bone marrow (FBM) is the central site of hematopoietic stem and progenitor cell (HSPC) development, and disruptions in this niche can have lifelong effects on immunity, infection susceptibility, and inflammatory disease risk. In this study, we examined FBM hematopoiesis in a nonhuman primate model of spontaneous maternal obesity. MethodsUsing spectral flow cytometry, single-cell RNA sequencing, and functional differentiation assays, we mapped progenitor composition, lineage trajectories, and immune function in offspring exposed to maternal obesity compared with lean controls. These complementary approaches allowed us to capture cellular frequencies and transcriptional programs, while trajectory and signaling analyses provided insight into how progenitor maturation and intercellular communication are disrupted by maternal obesity. ResultsOur findings reveal that maternal obesity decreases CD34+ HSPCs and common lymphoid progenitor populations, while expanding megakaryocyte-erythroid and granulocyte-monocyte progenitors. Pseudotime analysis demonstrated altered maturation, with cells accumulating at early differentiation states. Transcriptional profiling uncovered a strong inflammatory bias, with myeloid progenitors upregulating alarmins, interferon-stimulated genes, and proinflammatory mediators. Functionally, monocytes derived from obese FBM showed impaired migratory and colony-stimulating capacity, coupled with exaggerated TNF responses to LPS stimulation. ConclusionTogether, these results demonstrate that maternal obesity, even in the absence of obesogenic diet, disrupts fetal bone marrow hematopoiesis by altered HSPC maturation, reprogramming lineage trajectories, and inducing inflammatory bias.

immunology↗

bioRxiv2025

Maternal opioid use with and without hepatitis C infection disrupts the structure and immune landscape of the maternal-fetal interface

Maternal opioid use disorder (OUD) poses significant risks to maternal and fetal health. Adverse outcomes associated with maternal OUD are believed to be mediated, in part, by changes in placenta structure and function; however, few studies have addressed this question. Here, we utilized a combination of flow cytometry, histology, spatial and single-cell transcriptomics to uncover the impact of OUD on placental tissues. Given that nearly half of subjects with chronic OUD contract hepatitis C (HCV), we further stratified our findings by maternal HCV status. Our results indicate that maternal OUD leads to a higher incidence of vascular malperfusion accompanied by increased levels of inflammatory markers and dysregulated secretion of placental development factors. Furthermore, spatial transcriptomics revealed that maternal OUD disrupts the communication between trophoblasts and immune cells important for placental vascular development. Additionally, CellChat analysis revealed aberrant VEGF and FN1 signaling across trophoblast, endothelial, and myeloid cells. Processes associated with tissue homeostasis and repair were also downregulated across trophoblast and leukocytes. Frequencies and responses to ex-vivo stimulation of decidual macrophages and cytolytic NK cells, critical for tissue remodeling and fetal tolerance, were decreased. Finally, transcriptional analyses of placental leukocytes also indicate shifts towards more regulatory/tissue surveillant phenotypes. Altogether, these results highlight the significant disruptions to placental health by maternal OUD. One Sentence SummaryMaternal opioid use disorder {+/-} hepatitis C coinfection disrupts placental structure, immune function, and cell-cell communication.

immunology↗

bioRxiv2025

Chronic alcohol consumption enhances the differentiation capacity of hematopoietic stem and progenitor cells into osteoclast precursors

Chronic alcohol consumption (CAC) is associated with an enhanced risk of bone fracture, reduced bone density, and osteoporosis. We have previously shown using a rhesus macaque model of voluntary ethanol consumption that CAC induces functional, transcriptomic, and epigenomic changes in hematopoietic stem and progenitor cells (HSPCs) and their resultant monocytes/macrophages, skewing them towards a hyper-inflammatory response. Here, we extended those studies and investigated alterations in osteoclasts, which, in postnatal life, are differentiated from HSPCs and play a critical role in maintaining bone homeostasis. Analysis using spectral flow cytometry revealed a skewing of HSPCs towards granulocyte-monocyte progenitors (GMPs) with the CAC group that was in concordance with an increased number of colony-forming unit-granulocyte/macrophage (CFU-GM). Additionally, HSPCs from animals in the CAC group incubated with M-CSF and RANKL were more likely to differentiate into osteoclasts, as evidenced by increased Tartrate-Resistant Acid Phosphatase (TRAP) staining and bone resorption activity. Moreover, single-cell RNA sequencing of differentiated HSPCs identified three clusters of osteoclast precursors in the CAC group with enhanced gene expression in pathways associated with cellular response to stimuli, membrane trafficking, and vesicle-mediated transport. Collectively, these data show that CAC-derived hematopoietic progenitor cells exhibit a higher capacity to differentiate into osteoclast precursors. These findings provide critical insights for future research on the mechanisms by which CAC disrupts monopoiesis homeostasis and enhances osteoclast precursors, thereby contributing to reduced bone density.

cell biology↗

bioRxiv2025

Phenotypic and Functional Alterations in Peripheral Blood Mononuclear Cell-Derived Microglia in a Primate Model of Chronic Alcohol Consumption

Alcohol-induced dysregulation of microglial activity is associated with neuroinflammation, cognitive decline, heightened risk for neurodegenerative diseases, alcohol dependence, and escalation of alcohol drinking. Given the challenge of longitudinally sampling primary microglia, we optimized an in vitro method to differentiate peripheral blood mononuclear cells (PBMC) from non-human primates (NHP) into microglia-like cells (induced-microglia; iMGL). The iMGLs displayed transcriptional profiles distinct from those of monocyte progenitors and closely resembling those of primary microglia. Notably, morphological features showed that differentiated iMGLs derived from NHPs with chronic alcohol consumption (CAC) possessed a more mature-like microglial morphology. Additionally, dysregulation in key inflammatory and regulatory markers alongside increased baseline phagocytic activity was observed in CAC-derived IMGLs in the resting state. Phenotypic and functional assessments following LPS stimulation indicated the presence of an immune-tolerant phenotype and enrichment of a CD86+ hyper-inflammatory subpopulation in iMGLs derived from ethanol-exposed animals. Collectively, these findings demonstrate that in vitro differentiation of PBMC offers a minimally invasive approach to studying the impact of CAC on microglial function revealing that CAC reshapes both functional and transcriptional profiles of microglia.

neuroscience↗

bioRxiv2023

Mild/Asymptomatic Maternal SARS-CoV-2 Infection Leads to Immune Paralysis in Fetal Circulation and Immune Dysregulation in Fetal-Placental Tissues

Few studies have addressed the impact of maternal mild/asymptomatic SARS-CoV-2 infection on the developing neonatal immune system. In this study, we analyzed umbilical cord blood and placental chorionic villi from newborns of unvaccinated mothers with mild/asymptomatic SARS-CoV-2 infection during pregnancy using flow cytometry, single-cell transcriptomics, and functional assays. Despite the lack of vertical transmission, levels of inflammatory mediators were altered in cord blood. Maternal infection was also associated with increased memory T, B cells, and non-classical monocytes as well as increased activation. However, ex vivo responses to stimulation were attenuated. Finally, within the placental villi, we report an expansion of fetal Hofbauer cells and infiltrating maternal macrophages and rewiring towards a heightened inflammatory state. In contrast to cord blood monocytes, placental myeloid cells were primed for heightened antiviral responses. Taken together, this study highlights dysregulated fetal immune cell responses in response to mild maternal SARS-CoV-2 infection during pregnancy.

immunology↗

bioRxiv2023

Chronic alcohol consumption dysregulates innate immune response to SARS-CoV-2 in the lung

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. Moreover, 9 million Americans engaged in binge or chronic heavy drinking (CHD) in 2019. CHD negatively impacts pathogen clearance and tissue repair, including in the respiratory tract, thereby increasing susceptibility to infection. Although, it has been hypothesized that chronic alcohol consumption negatively impacts COVID-19 outcomes; the interplay between chronic alcohol use and SARS-CoV-2 infection outcomes has yet to be elucidated. Therefore, in this study we investigated the impact of chronic alcohol consumption on SARS-CoV-2 anti-viral responses in bronchoalveolar lavage cell samples from humans with alcohol use disorder and rhesus macaques that engaged in chronic drinking. Our data show that in both humans and macaques, the induction of key antiviral cytokines and growth factors was decreased with chronic ethanol consumption. Moreover, in macaques fewer differentially expressed genes mapped to Gene Ontology terms associated with antiviral immunity following 6 month of ethanol consumption while TLR signaling pathways were upregulated. These data are indicative of aberrant inflammation and reduced antiviral responses in the lung with chronic alcohol drinking.

immunology↗

bioRxiv2023

Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow niche

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. Bone marrow-resident monocytes/macrophages from ethanol-consuming animals exhibited heightened inflammation. Differentiation of HSCP in vitro revealed skewing towards monocytes expressing neutrophil-like markers with heightened inflammatory responses to bacterial agonists. Single cell transcriptional analysis of HSCPs showed reduced proliferation but increased inflammatory markers in mature myeloid progenitors. We observed transcriptional signatures associated with increased oxidative and cellular stress as well as oxidative phosphorylation in immature and mature myeloid progenitors. Single cell analysis of the chromatin landscape showed altered drivers of differentiation in monocytes and progenitors. Collectively, these data indicate that chronic ethanol drinking results in remodeling of the transcriptional and epigenetic landscapes of the bone marrow compartment leading to altered functions in the periphery.

immunology↗

bioRxiv2023

Impact of aging on the immunological and microbial landscape of the lung during non-tuberculous mycobacterial infection

Nontuberculous mycobacteria (NTM) are environmentally ubiquitous and predominately cause pulmonary disease (NTMPD). The incidence of NTMPD has steadily increased and is now more prevalent than that of Mycobacterium tuberculosis (M. tb) in the US. Moreover, the prevalence of NTMPD increases with age; therefore, it is likely that the burden of NTMPD will continue to increase in the coming decades as the number of those over the age of 65 increased in the U.S population. However, the mechanisms leading to higher susceptibility and severity of NTMPD with aging are poorly defined. Here, we used a rhesus macaque model of intrabronchial infection with M. avium complex in young and aged animals to address this knowledge gap. Unilateral infection resulted in a robust inflammatory response predominantly in the inoculated lung, however, immune cell infiltration and antigen-specific T cell responses were detected in both lungs. Nasal, oral, and fecal swabs, and BAL samples were profiled using 16S amplicon sequencing. These data suggested that decompartmentalization of the lower respiratory microbiome was occurring, evidenced by detection of bacterial DNA typically found in the gut and oral-pharyngeal cavity in bronchoalveolar samples following infection. Radiographic studies, gross pathology, and histopathology examination revealed increased disease severity in aged compared to young animals with pulmonary consolidation, edema, and lesions. Finally, single cell RNA sequencing indicated that aged animals generated a dysregulated macrophage and CD8 T cell response to MAC infection.

immunology↗

bioRxiv2022

SARS-CoV-2 Vaccine Booster Elicits Robust Prolonged Maternal Antibody Responses and Passive Transfer Via The Placenta And Breastmilk

BackgroundInfection during pregnancy can result in adverse outcomes for both pregnant persons and offspring. Maternal vaccination is an effective mechanism to protect both mother and neonate into post-partum. However, our understanding of passive transfer of antibodies elicited by maternal SARS-CoV-2 mRNA vaccination during pregnancy remains incomplete. ObjectiveWe aimed to evaluate the antibody responses engendered by maternal SARS-CoV-2 vaccination following initial and booster doses in maternal circulation and breastmilk to better understand passive immunization of the newborn. Study DesignWe collected longitudinal blood samples from 121 pregnant women who received SARS-CoV-2 mRNA vaccines spanning from early gestation to delivery followed by collection of blood samples and breastmilk between delivery and 12 months post-partum. During the study, 70% of the participants also received a booster post-partum. Paired maternal plasma, breastmilk, umbilical cord plasma, and newborn plasma samples were tested via enzyme-linked immunosorbent assays (ELISA) to evaluate SARS-CoV-2 specific IgG antibody levels. ResultsVaccine-elicited maternal antibodies were detected in both cord blood and newborn blood, albeit at lower levels than maternal circulation, demonstrating transplacental passive immunization. Booster vaccination significantly increased spike specific IgG antibody titers in maternal plasma and breastmilk. Finally, SARS-CoV-2 specific IgG antibodies in newborn blood correlated negatively with days post initial maternal vaccine dose. ConclusionVaccine-induced maternal SARS-CoV-2 antibodies were passively transferred to the offspring in utero via the placenta and after birth via breastfeeding. Maternal booster vaccination, regardless of gestational age at maternal vaccination, significantly increased antibody levels in breastmilk and maternal plasma, indicating the importance of this additional dose to maximize passive protection against SARS-CoV-2 infection for neonates and infants until vaccination eligibility.

immunology↗

bioRxiv2022

Multimodal profiling of term human decidua reveals tissue-specific immune adaptations with maternal obesity

The leukocyte diversity of early maternal-fetal interface has been recently described, however, characterization of decidua at term is still pending. We, therefore, profiled the CD45+ compartment within human term decidua collected via cesarean section. Relative to the first trimester, our analyses revealed a shift from NK cells and macrophages to T-cells and enhanced activation of all immune cells. T-cells in the decidua were phenotypically distinct from their blood counterparts and demonstrated significant clonotype sharing. Using pseudo-temporal analyses of macrophages, we characterize previously undescribed diversity of bonafide tissue resident decidual macrophages. The frequency of this population correlated with high pregravid maternal body mass index but responded poorly to bacteria ligands. Collectively, these findings provide evidence of skewing of decidual myeloid cells towards immunoregulation representing a possible mechanism to safeguard the fetus. This immune cell atlas of term decidua is an asset for future studies investigating pathological conditions that compromise reproductive success. One sentence summaryHuman immune cell atlas of term decidua and observed alterations with pre-gravid obesity.

immunology↗

bioRxiv2022

Impact of pregravid obesity on anti-microbial fetal monocyte response

Maternal pre-pregnancy (pregravid) obesity is associated with adverse outcomes for both mother and offspring. Amongst the complications for the offspring is increased susceptibility and severity of neonatal infections necessitating admission to the intensive care unit, notably bacterial sepsis and enterocolitis. Previous studies have reported aberrant responses to LPS and polyclonal stimulation by umbilical cord blood monocytes that were mediated by alterations in the epigenome. In this study, we show that pregravid obesity dysregulates umbilical cord blood monocyte responses to bacterial and viral pathogens. Specifically, interferon-stimulated gene expression and inflammatory responses to E. coli and respiratory syncytial virus (RSV) were significantly dampened. Although upstream signaling events were comparable, translocation of the key transcription factor NF-{kappa}B and chromatin accessibility at pro- inflammatory gene promoters following TLR stimulation was significantly attenuated. Using a rhesus macaque model of western style diet induced obesity, we further demonstrate that this defect is detected in fetal peripheral monocytes and tissue-resident macrophages during gestation. Collectively, these data indicate that maternal obesity and high-fat diet present metabolic, signaling, and epigenetic impediments to pathogen recognition in fetal innate immune cells that result in a state of immune paralysis during gestation and at birth.

immunology↗

bioRxiv2022

Therapeutic neutralizing monoclonal antibody administration protects against lethal viscerotropic Yellow Fever infection

Few countermeasures to treat Yellow Fever virus (YFV) infection are under development, because vaccines have helped to limit new infections. Unfortunately, vaccine hesitancy, supply deficits, and a paucity of therapeutic options have left individuals at risk. Here, we tested potent YFV-specific neutralizing monoclonal antibodies in rodents and non-human primates. We administered antibodies during acute pathogenic YFV infection and demonstrate that we can prevent severe disease and death. Given the severity of YFV-induced disease, our results show that these antibodies could be effective in saving lives and fill a much-needed void in managing Yellow Fever cases during outbreaks around the world. One Sentence SummaryTherapeutic monoclonal antibodies prevent death from YFV infection.

immunology↗

bioRxiv2022

Taxonomic and functional shifts in the perinatal gut microbiome of rhesus macaques

Pregnancy and the postpartum period result in some of the most dramatic metabolic, hormonal, and physiological changes that can be experienced by an otherwise healthy adult. The timing and magnitude of these changes is key for both maternal and fetal health. One of the factors believed to critically modulate these physiological changes is the maternal gut microbiome. However, the dynamic changes in this community during the perinatal period remain understudied. Clinical studies can be complicated by confounding variables such as diet and other drivers of heterogeneity in the human microbiome. Therefore, in this study, we conducted a longitudinal analysis of the fecal microbiome obtained during the perinatal and post-partum periods in 25 rhesus macaques using 16S rRNA gene amplicon sequencing and shotgun metagenomics. Shifts at both the taxonomic and functional potential level were detected when comparing pregnancy to postpartum samples. Taxonomically, Alloprevotella, Actinobacillus, and Anaerovibrio were enriched during pregnancy while Treponema, Lachnospiraceae, and Methanosphaera were more abundant post-partum. Functionally, pregnancy was associated with increased abundance in the pathway to produce the beneficial short chain fatty acid (SCFA), butyrate, while pathways associated with starch degradation and folate transformation were more abundant postpartum. These data demonstrate dramatic changes in the maternal gut even in the absence of dietary changes and suggest that rhesus macaques could provide a valuable model to determine how changes in the microbiome correlate to other physiological changes in pregnancy.

microbiology↗

bioRxiv2022

Functional, transcriptional, and microbial shifts associated with healthy pulmonary aging: insights from rhesus macaques

Older individuals are at increased risk of developing severe respiratory infections due to age-related changes in the immunological, microbial, and functional landscape of the lung. However, our understanding of the impact of age on the respiratory tract remains limited as samples from healthy humans are challenging to obtain and confounding variables such as smoking and environmental pollutant exposure make it difficult to assess the true impact of aging. On the other hand, studies in rodent models are biased by their specific pathogen free status. In this study, we utilize a rhesus macaque model of healthy aging to examine the functional, immunological, and microbial consequences of aging in the lung. Pulmonary function testing in this large (n=34 adult, n=49 aged) cross-sectional study established age and sex differences similar to humans supporting the translational accuracy of this model. Additionally, an increased abundance of myeloid cells (alveolar and infiltrating macrophages) and a concomitant decrease in T-cells were also observed in aged animals. Single cell RNA sequencing indicated a transcriptional shift in the pulmonary CD8+ T-cell population from GRZMB expressing cells to IFN expressing cells, while frequency of IL-1B expressing alveolar macrophages was significantly reduced. Interestingly, the lung microbiome of many animals was dominated by a single microbe, Tropheryma spp., the prevalence of which decreased with age. These data provide a comprehensive picture of the functional, microbial and immunological changes of the lung in healthy macaque aging and provide insight into the increased prevalence and severity of respiratory disease in the elderly.

immunology↗

bioRxiv2021

Deep immune profiling of the maternal-fetal interface with mild SARS-CoV-2 infection

Pregnant women are an at-risk group for severe COVID-19, though the majority experience mild/asymptomatic disease. Although severe COVID-19 has been shown to be associated with immune activation at the maternal-fetal interface even in the absence of active viral replication, the immune response to asymptomatic/mild COVID-19 remains unknown. Here, we assessed immunological adaptations in both blood and term decidua from 9 SARS-exposed pregnant women with asymptomatic/mild disease and 15 pregnant SARS-naive women. In addition to selective loss of tissue-resident decidual macrophages, we report attenuation of antigen presentation and type I IFN signaling but upregulation of inflammatory cytokines and chemokines in blood monocyte derived decidual macrophages. On the other hand, infection was associated with remodeling of the T cell compartment with increased frequencies of activated CD69+ tissue-resident T cells and decreased abundance of Tregs. Interestingly, frequencies of cytotoxic CD4 and CD8 T cells increased only in the blood, while CD8 effector memory T cells were expanded in the decidua. In contrast to decidual macrophages, signatures of type I IFN signaling were increased in decidual T cells. Finally, T cell receptor diversity was significantly reduced with infection in both compartments, albeit to a much greater extent in the blood. The resulting aberrant immune activation in the placenta, even with asymptomatic disease may alter the exquisitely sensitive developing fetal immune system, leading to long-term adverse outcomes for offspring.

immunology↗

bioRxiv2021

Chronic ethanol drinking in non-human primates induces inflammatory cathepsin gene expression in alveolar macrophages accompanied by functional defects

Chronic alcohol drinking is associated with increased susceptibility to viral and bacterial respiratory pathogens. Investigating the effects of alcohol on the lung is challenging in humans because of the complexity of human drinking behavior and the challenge of obtaining samples. In this study, we utilize a rhesus macaque model of voluntary ethanol self-administration to study the effects of alcohol on the lung in a physiologically and genetically relevant model. We report a heightened activation and inflammatory state in alveolar macrophages (AM) obtained from ethanol 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. In line with these transcriptional and epigenetic changes at basal state, AM from ethanol drinking animals generate elevated inflammatory mediator responses to LPS and respiratory syncytial virus (RSV). Analysis using scRNA-Seq revealed heterogeneity in lung-resident macrophage and monocyte populations, including increased abundance of activated and cathepsin-expressing clusters and accelerated differentiation with ethanol. Finally, functional assays show increased mitochondrial content in AM from ethanol drinking animals, which is associated with observed increased ROS and decreased phagocytosis capacity. This comprehensive epigenomic, transcriptional and functional profiling of lung macrophages after ethanol drinking in macaques provides previously unidentified mechanisms of ethanol induced infection susceptibility in patients with alcohol use disorders.

immunology↗

bioRxiv2021

Exploratory extracellular vesicle-bound miRNA profiling to identify candidate biomarkers of chronic alcohol drinking in non-human primates

BackgroundLong-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 is challenging to determine whether alcohol use should be considered a risk factor during diagnosis and treatment. We lack reliable biomarkers of alcohol use that could be used to determine drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNA (EV-miRNA) have been discovered to be consistent biomarkers of conditions including cancer and liver disease. MethodsIn this study, we profiled the plasma EV-miRNA content by miRNA-Seq from 80 non-human primates after 12 months of voluntary ethanol drinking. ResultsWe identified a list of up- and downregulated EV-miRNA candidate biomarkers of both heavy drinking as well as those positively correlated with ethanol dose. We further overexpressed these candidate miRNA in control primary peripheral immune cells to assess potential functional mechanisms of these EV-miRNA. We identified that overexpression of miR-155, miR-154, miR-34c, miR-450a, and miR-204 led to increased inflammatory TNF or IL-6 production in PBMC after stimulation. ConclusionThis exploratory study identified several EV-miRNA that could serve as biomarkers of long-term alcohol drinking as well as provided a mechanism for alcohol-induced peripheral inflammation.

molecular biology↗