Functional and Transcriptional Adaptations of Blood Monocytes Recruited to the Cystic Fibrosis Airway Microenvironment In Vitro
| Autor: | Diego Moncada Giraldo, Limin Peng, Rabindra Tirouvanziam, Bijean D Ford, Camilla Margaroli, Milton R. Brown, Vincent D. Giacalone |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Chemokine lung disease Cystic Fibrosis Transcription Genetic Neutrophils Biology Cystic fibrosis Article Monocytes Catalysis Inorganic Chemistry lcsh:Chemistry 03 medical and health sciences 0302 clinical medicine In vivo medicine Humans CXCL11 Physical and Theoretical Chemistry Scavenger receptor bacteria Lung Molecular Biology transmigration lcsh:QH301-705.5 Cells Cultured Spectroscopy Monocyte Organic Chemistry General Medicine scavenging medicine.disease Adaptation Physiological In vitro Computer Science Applications 030104 developmental biology medicine.anatomical_structure Cellular Microenvironment 030228 respiratory system lcsh:Biology (General) lcsh:QD1-999 Immunology biology.protein Female Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 2530, p 2530 (2021) International Journal of Molecular Sciences Volume 22 Issue 5 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Cystic fibrosis (CF) lung disease is dominated by the recruitment of myeloid cells (neutrophils and monocytes) from the blood which fail to clear the lung of colonizing microbes. In prior in vitro studies, we showed that blood neutrophils migrated through the well-differentiated lung epithelium into the CF airway fluid supernatant (ASN) mimic the dysfunction of CF airway neutrophils in vivo, including decreased bactericidal activity despite an increased metabolism. Here, we hypothesized that, in a similar manner to neutrophils, blood monocytes undergo significant adaptations upon recruitment to CFASN. To test this hypothesis, primary human blood monocytes were transmigrated in our in vitro model into the ASN from healthy control (HC) or CF subjects to mimic in vivo recruitment to normal or CF airways, respectively. Surface phenotype, metabolic and bacterial killing activities, and transcriptomic profile by RNA sequencing were quantified post-transmigration. Unlike neutrophils, monocytes were not metabolically activated, nor did they show broad differences in activation and scavenger receptor expression upon recruitment to the CFASN compared to HCASN. However, monocytes recruited to CFASN showed decreased bactericidal activity. RNASeq analysis showed strong effects of transmigration on monocyte RNA profile, with differences between CFASN and HCASN conditions, notably in immune signaling, including lower expression in the former of the antimicrobial factor ISG15, defensin-like chemokine CXCL11, and nitric oxide-producing enzyme NOS3. While monocytes undergo qualitatively different adaptations from those seen in neutrophils upon recruitment to the CF airway microenvironment, their bactericidal activity is also dysregulated, which could explain why they also fail to protect CF airways from infection. |
| Databáze: | OpenAIRE |
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