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Single cells RNA sequencing of peripheral blood mononuclear cells reveals that hyperinflammatory monocytes are associated with Mycobaterium abscessus pulmonary disease

ABSTRACT: Rationale: Nontuberculous mycobacteria (NTM) infection can promote progressive lung function decline and damage, a condition known as NTM Pulmonary Disease (NTM-PD). Mycobacterium abscessus complex (MABSC) is a common cause of infections in people with cystic fibrosis (pwCF). Here, we performed the first single-cell transcriptome characterization of circulating cellular transcripts in pwCF at risk of MABSC infections. Objectives: To define the circulating immune transcriptional profiles of pwCF with MABSC colonization or MABSC pulmonary disease. Methods: We isolated peripheral blood mononuclear cell (PBMCs) and blood plasma of 12 pwCF including those displayed MABSC colonization or pulmonary disease and those with no history of NTM detection as control group. To identify immune signatures, we performed single cell (sc)RNA-sequencing and Luminex assay and validate our findings publicpublicly available datasets. Measurements and Main Results: We determined 10 cells populations annotated according to the expression levels and performed differentially expressed genes analysis among the three groups in each cellular population. We found out that pwCF with active MABSC pulmonary disease showed i) a set of transcripts specifically upregulated in CD14+ and CD16+ monocytes, ii) a downregulation of expression profiles related to NK and CD8 T cellular clusters, iii) the identified CD14+ monocytes characterized by IFNs signalling and pro-inflammatory pathways. In addition, we confirmed the highest CXCL10 levels in pwCF with pulmonary disease. Moreover, we validated our findings in a second publicpublicly available datasets from a cohort of pwCF infected by MABSC. Conclusions: Overall, we applyedapplied scRNAseq technologies to circulating blood cells and defined that circulating hyperinflammatory monocyte responses are associated to MABSC pulmonary disease in pwCF.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234785 | GEO | 2024/09/18

REPOSITORIES: GEO

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Project description:A major population of placenta macrophages represented throughout the pregnancy consists of CD14+ macrophages, but their characteristics remain badly understood. Here we purified from placentas at term CD14+ macrophages using positive selection. The phenotyping of CD14+ macrophages performed using flow cytometry revealed that placenta CD14+ macrophages expressed a series of markers distinct of those of circulating monocytes monocyte-derived macrophages. Placenta CD14+ macrophages spontaneously matured in multinucleated giant cells (MGCs) as demonstrated by size, number of nuclei display and specific cytoskeleton organization. Placenta CD14+ macrophages and MGCs were phagocytic cells but the potential of MGCs to mount an inflammatory response was lower than that of their precursors. Placenta CD14+ macrophages and MGCs stimulated with interferon and interleukin-4 were not polarized into typical M1 or M2 profiles. Placenta macrophages exhibited specific activation transcriptional programs. Indeed, principal component analysis and hierarchical clustering show that placental macrophages formed a distinct group from circulating monocytes and monocyte-derived macrophages. Among placenta macrophages, it was also possible to distinguish CD14+ macrophages and MGCs. In addition, networks based on gene interactions were clearly different in CD14+ macrophages and MGCs. Finally, the microenvironment of placenta CD14+ macrophages governs their differentiation into MGCs because CD14+ macrophages incubated with trophoblasts exhibited exarcerbated characteristics of MGCs and because the co-incubation of circulating monocytes from working women with trophoblast supernatants resulted into the formation of MGCs whereas monocytes from non-pregnant women incubated with trophoblast supernatants did not differentiate into MGCs. Taken together, these results clearly demonstrated specific feaures of placenta CD14+ macrophages. Three replicates of each of the following: 1. Placental macrophages just after isolation (CD14+ macrophages) 2. Placental macrophages after 9 days in culture (MGCs) 3. CD14+ cells isolated from PBMC which are extracted from the whole human blood of healthy donors (Monocytes) 4. Macrophages derived from monocytes (MDMs)

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Single cells RNA sequencing of peripheral blood mononuclear cells reveals that hyperinflammatory monocytes are associated with Mycobaterium abscessus pulmonary disease

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