ScRNA-seq analysis of CD11c+ cells from bronchoalveolar lavage fluid during the IAV (PR/8, H1N1) infection course
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE208294 | GEO | 2023/11/20
REPOSITORIES: GEO
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Project description:Background: Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are two most frequent forms of interstitial lung diseases (ILDs). Cellular and biochemical composition of bronchoalveolar lavage fluid (BALf) was shown to reflect the proliferative and fibrotic changes in the local environment in the lung. However, the usefulness of BALf cellular profile evaluation in the diagnosis of ILDs is limited. The aim of the study was a multivariate, molecular, comparative analysis of BALf cells from IPF and sarcoidosis patients. Methods: Transcriptomic measurements were carried out using Affymetrix Human Gene 2.1 ST ArrayStrip in 21 samples: 9 IPF and 12 sarcoidosis. The mRNA expression for the most significantly differentiating genes was evaluated by real time PCR in 32 samples (11 IPF and 21 sarcoidosis). Results: The number of genes differentially expressed between IPF and sarcoidosis groups were 4832 (13359 probesets). Our cluster analysis indicated that sarcoidosis BALf cells are characterized by increased mRNA expression of genes associated with ribosome biogenesis, transcription machinery. Clusters formed by genes with changed mRNA expression in IPF samples were implicated in the processes of cell adhesion and migration, metalloproteinase expression and negative regulation of cell proliferation. PCR verification showed higher expression of ANK3 in the sarcoidosis compared to the IPF group, and higher expression of MMP7 and PPBP in patients with IPF. The GO analysis indicated that predominant biological processes associated with the differential mRNA gene expression of BALf cells were upregulation of neutrophils in IPF and lymphocytes in sarcoidosis. Conclusions: Analysis of BALf from sarcoidosis and IPF showed highly different mRNA profile of cells present in bronchoalveolar compartment and provided new data on the pathobiology of these ILDs. The changes of most important biological processes observed at the molecular level in BALf cells were associated with ribosome biogenesis and proteasome apparatus in sarcoidosis and neutrophilic dysfunction in IPF.
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Project description:Bronchoalveolar lavage is commonly performed to examine inflammation and responsible pathogens in lung diseases, and its findings may be used to assess the immune profile of the lung tumor microenvironment (TME). To investigate whether analyses of bronchoalveolar lavage fluid (BALF) can help identify non-small cell lung cancer (NSCLC) patients who respond to immune checkpoint inhibitors (ICIs), BALF and blood were prospectively collected before initiating nivolumab. The secreted molecules, microbiome, and cellular profiles based on BALF and blood analysis were compared regarding therapeutic effect in 12 patients. Compared to non-responders, responders showed significantly higher CXCL9 levels and greater diversity in the lung microbiome profile in BALF, and greater frequency of CD56+ subset in blood T cells, whereas no significant difference was found in PD-L1 expression of tumor cells. Antibiotic treatment in a preclinical lung cancer model significantly decreased CXCL9 in the lung TME, resulting in reduced sensitivity to nivolumab, which was reversed by CXCL9 induction in tumor cells. Thus, CXCL9 and the microbiome in the lung TME might be associated with each other, and their balance could contribute to nivolumab sensitivity in NSCLC patients. BALF analysis can help predict the efficacy of ICIs when performed along with currently approved examinations.
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Project description:Immune characteristics associated with Coronavirus Disease-2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid (BALF) immune cells from patients with varying severity of COVID-19 disease and from healthy subjects using single-cell RNA-sequencing. Proinflammatory monocyte-derived macrophages were abundant in the BALF from severe COVID-9 patients. Moderate cases were characterized by the presence of highly clonally expanded tissue-resident CD8+ T cells. This atlas of the bronchoalveolar immune-microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.
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Project description:Bronchoalveolar Lavage cells include resident and infiltrating immune cells in repsone to infections. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of BALF cells.
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Project description:The analysis of bronchoalveolar lavage fluid (BALF) using mass spectrometry-based metabolomics can provide insight into lung diseases, such as asthma. However, the important step of compound identification is hindered by the lack of a small molecule database that is specific for BALF. Here we describe prototypic, small molecule databases derived from human BALF samples (n=117). Human BALF was extracted into lipid and aqueous fractions and analyzed using liquid chromatography mass spectrometry. Following filtering to reduce contaminants and artifacts, the resulting BALF databases (BALF-DBs) contain 11,737 lipid and 658 aqueous compounds. Over 10% of these were found in 100% of samples. Testing the BALF-DBs using nested test sets produced a 99% match rate for lipids and 47% match rate for aqueous molecules. Searching an independent dataset resulted in 45% matching to the lipid BALF-DB compared to < 25% when general databases are searched. Overall, the BALF-DBs can reduce false positives and improve confidence in compound identification compared to when general databases are used.
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Project description:Comprehensive proteomic analysis of the protein expression landscape of bronchoalveolar lavage fluid during invasive pulmonary aspergillosis in murine and human samples. 38 murine BALF samples (10 Aspergillus fumigatus infected mice without immunosuppression and without invasive pulmonary aspergillosis (IPA), 19 immunosuppressed and infected mice with IPA and 9 immunosuppressed animals without infection) were analysed for their global protein expression. In addition, 54 human BALF specimen from patients with probable IPA (23 samples), proven IPA (4 cases) and 27 control samples from patients with unrelated pulmonary diseases were analysed for their global protein composition. Host responses and Aspergillus fumigatus-specific proteins detectable in BALF were studied.
2020-10-14 | PXD016664 | Pride
Project description:Rationale: Alveolar macrophages (AM) are functionally important innate cells involved in lung homeostasis and immunity. However, it remains unclear whether ontogenically and functionally distinct subpopulations of AM can be found in healthy human airways, and to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Objective: To explore the phenotypical, ontological, transcriptional and functional diversity of human AM isolated from healthy non-smokers, healthy smokers and COPD patients. Methods: We analyzed bronchoalveolar lavage fluid (BALF) cells by flow cytometry, bulk and single-cell(sc) RNA-sequencing (RNA-seq). Main Results: We found that BALF CD206 + macrophage subpopulations could be distinguished based on their level of auto-fluorescence. CD206 + autofluorescent high (AF hi ) AM were identified as classical self-proliferative AM, while autofluorescent low (AF lo ) AM originated from monocytes and were expressing both monocyte- and classical AM-related genes. Of note, monocyte-derived AF lo AM were equally represented in each category of subjects and exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine interleukin-10 (IL-10). Finally, we provide evidence that the monocyte-associated marker CCR2 can be used by flow cytometry to distinguish AM according to their origin.
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Project description:Recent progress in unbiased metagenomic next-generation sequencing (mNGS) allows simultaneous examination of microbial and host genetic material in a single test. Leveraging affordable bronchoalveolar lavage fluid (BALF) mNGS data, we employed machine learning to create a diagnostic approach distinguishing lung cancer from pulmonary infections, conditions prone to misdiagnosis in clinical settings. This prospective study analyzed BALF-mNGS data from lung cancer and pulmonary infection patients, delineating differences in DNA/RNA microbial composition, bacteriophage abundances, and host responses, including gene expression, transposable element levels, immune cell composition, and tumor fraction derived from copy number variation (CNV). Integrating these metrics into a host/microbe metagenomics-driven machine learning model (Model VI) demonstrated robustness, achieving an AUC of 0.87 (95% CI = 0.857-0.883), sensitivity = 73.8%, and specificity = 84.5% in the training cohort, and an AUC of 0.831 (95% CI = 0.819-0.843), sensitivity = 67.1%, and specificity = 94.4% in the validation cohort for distinguishing lung cancer from pulmonary infections. The application of a rule-in and rule-out strategy-based composite predictive model significantly enhances accuracy (ACC) in distinguishing between lung cancer and tuberculosis (ACC=0.913), fungal infection (ACC=0.955), and bacterial infection (ACC=0.836). These findings highlight the potential of cost-effective mNGS-based analysis as a valuable tool for early differentiation between lung cancer and pulmonary infections, offering significant benefits through a single comprehensive testing.
2024-01-08 | GSE252118 | GEO
Project description:Rationale: Airspace macrophages are the most abundant cell in airspaces and are viewed as a homogeneous population during health. Single cell RNA sequencing allows for examination of transcriptional heterogeneity between cells and between individuals. Understanding the conserved repertoire of airspace leukocytes during health is essential to understanding cellular programing during disease. Objective: We sought to determine the transcriptional heterogeneity of human bronchoalveolar lavage cells in healthy adults. Methods: Ten healthy subjects underwent bronchoscopy. Cells obtained from lavage fluid were subjected to single cell RNA sequencing. Unique cell populations and putative functions were identified. Transcriptional profiles were compared across individuals. Measurements and Main Results: Based on transcriptional profiling we identify highly conserved macrophage, monocyte-like, lymphocyte, dendritic cell, and cycling cell populations. We define two unique subgroups of resident airspace macrophages - one defined by a pro-inflammatory profile and one by metallothionein gene expression. We identify distinct subsets of monocyte-like cells and directly compared them to peripheral blood mononuclear cells. Finally, we compare global macrophage and monocyte programing between male and female subjects. Conclusions: Healthy human airspaces contain multiple populations of leukocytes that are highly conserved between individuals and between the sexes. Resident macrophages comprise the largest population and include novel subsets defined by inflammatory and metal-binding gene signatures. Monocyte-like cells within the airspaces are transcriptionally distinct from circulating blood cells and include a rare population defined by expression of cell-matrix interaction genes. This study is the first to define airspace immune cell heterogeneity and identifies three previously unrecognized myeloid cell subsets.
2020-10-21 | GSE151928 | GEO
Project description:Rationale: Alveolar macrophages (AM) are functionally important innate cells involved in lung homeostasis and immunity. However, it remains unclear whether ontogenically and functionally distinct subpopulations of AM can be found in healthy human airways, and to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Objective: To explore the phenotypical, ontological, transcriptional and functional diversity of human AM isolated from healthy non-smokers, healthy smokers and COPD patients. Methods: We analyzed bronchoalveolar lavage fluid (BALF) cells by flow cytometry, bulk and single-cell(sc) RNA-sequencing (RNA-seq). Main Results: We found that BALF CD206 + macrophage subpopulations could be distinguished based on their level of auto-fluorescence. CD206 + autofluorescent high (AF hi ) AM were identified as classical self-proliferative AM, while autofluorescent low (AF lo ) AM originated from monocytes and were expressing both monocyte- and classical AM-related genes. Of note, monocyte-derived AF lo AM were equally represented in each category of subjects and exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine interleukin-10 (IL-10). Finally, we provide evidence that the monocyte-associated marker CCR2 can be used by flow cytometry to distinguish AM according to their origin.
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