Cystic Fibrosis Plasma Blunts the Immune Response to Bacterial Infection. Am J Respir Cell Mol Biol 2019 Sep;61(3):301-311
Date
03/09/2019Pubmed ID
30848661Pubmed Central ID
PMC6839930DOI
10.1165/rcmb.2018-0114OCScopus ID
2-s2.0-85071755620 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Cystic fibrosis (CF) is caused by mutations of the gene encoding the CF transmembrane conductance regulator. It remains unclear whether the abnormal immune response in CF involves extrinsic signals released from the external or internal environment. We sought to characterize the peripheral immune signatures in CF and its association with clinical phenotypes. Healthy peripheral blood mononuclear cells (PBMCs) were cultured with plasma from CF probands (CFPs) or healthy control subjects (HCs) followed by nCounter gene and microRNA (miRNA) profiling. A discovery cohort of 12 CFPs and 12 HCs and a validation cohort of 103 CFPs and 31 HCs (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. 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. Extrinsic signals in plasma from patients with CF led to monocyte inactivation and miRNA upregulation in PBMCs. 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.
Author List
Zhang X, Pan A, Jia S, Ideozu JE, Woods K, Murkowski K, Hessner MJ, Simpson PM, Levy HAuthors
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of WisconsinAmy Y. Pan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Katherine Woods in the CTSI department at Medical College of Wisconsin - CTSI
MESH terms used to index this publication - Major topics in bold
Bacterial InfectionsCells, Cultured
Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
Humans
Leukocytes, Mononuclear
Lung
MicroRNAs
Monocytes
Plasma
Pseudomonas Infections
Pseudomonas aeruginosa
