Cystic Fibrosis Plasma Blunts the Immune Response to Bacterial Infection.
Am J Respir Cell Mol Biol. 2019 Mar 08;:
Authors: Zhang X, Pan A, Jia S, Ideozu JE, Woods K, Murkowski K, Hessner MJ, Simpson PM, Levy H
RATIONALE: Cystic fibrosis (CF) is caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). It remains unclear whether the abnormal immune response in CF involves extrinsic signals released from the external or internal environment.
OBJECTIVES: To characterize the peripheral immune signatures in CF and its association with clinical phenotypes.
METHODS: Healthy peripheral blood mononuclear cells (PBMCs) were cultured with plasma from CF probands (CF) or healthy controls (HC) followed by nCounter gene and microRNA (miRNA) profiling. A discovery cohort of 12 CF and 12 HC and a validation cohort of 103 CF and 31 HC (our previous microarray data, GSE71799) were analyzed to characterize the composition of cultured immune cells and establish a miRNA‒mRNA network. Cell compositions and miRNA profiles were associated with clinical characteristics of the cohorts.
MEASUREMENTS AND MAIN RESULTS: Significantly differentially expressed genes and abundance of myeloid cells were downregulated in PMBCs after culture with CF plasma (p < 0.05). Top-ranked miRNAs that increased in response to CF plasma (adjusted p < 0.05) included miR-155 and miR-146a, which target many immune-related genes such as IL-8. Pseudomonas aeruginosa infection was negatively associated with abundance of monocytes and the presence of those regulatory miRNAs. CONCLUSIONS: Extrinsic signals in plasma from CF patients led to monocyte inactivation and miRNA upregulation in PBMC. An improved understanding of the immune effects of extrinsic factors in CF holds great promise for integrating immunomodulatory cell therapies into current treatment strategies in CF. PMID: 30848661 [PubMed - as supplied by publisher] PubMed:30848661