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

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.