Granulocytic Myeloid-Derived Suppressor Cells in Cystic Fibrosis.

Samantha L Tucker,Balázs Rada,Demba Sarr

doi:10.3389/fimmu.2021.745326

Samantha L Tucker, Balázs Rada + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2021.745326

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Journal: Frontiers in Immunologie	Publication Date: Sep 21, 2021
Citations: 9	License type: CC BY 4.0

Affiliation: University of Georgia

Abstract

Cystic Fibrosis (CF) is a genetic disease that causes chronic and severe lung inflammation and infection associated with high rates of mortality. In CF, disrupted ion exchange in the epithelium results in excessive mucus production and reduced mucociliary clearance, leading to immune system exacerbation and chronic infections with pathogens such as P. aeruginosa and S. aureus. Constant immune stimulation leads to altered immune responses including T cell impairment and neutrophil dysfunction. Specifically, CF is considered a Th17-mediated disease, and it has been proposed that both P. aeruginosa and a subset of neutrophils known as granulocytic myeloid suppressor cells (gMDSCs) play a role in T cell suppression. The exact mechanisms behind these interactions are yet to be determined, but recent works demonstrate a role for arginase-1. It is also believed that P. aeruginosa drives gMDSC function as a means of immune evasion, leading to chronic infection. Herein, we review the current literature regarding immune suppression in CF by gMDSCs with an emphasis on T cell impairment and the role of P. aeruginosa in this dynamic interaction.

Highlights

Cystic Fibrosis (CF) is considered a Th17-mediated disease, and it has been proposed that both P. aeruginosa and a subset of neutrophils known as granulocytic myeloid suppressor cells play a role in T cell suppression
This paper examined the role of cftr in granulocytic myeloid suppressor cells (gMDSCs) function, and showed a slight impairment of T cell suppression in cftr-/- gMDSCs; this impairment only occurred at very high gMDSC to T cell ratios, suggesting that cftr is only minimally involved in T cell suppression by gMDSCs [18, 19]
This study demonstrates that gMDSCs are intrinsic to a CF mouse model, but that P. aeruginosa infection is involved in gMDSC recruitment to the lungs and T cell suppression [18]

Summary

Introduction

Cystic Fibrosis (CF) is a genetic disease that causes chronic and severe lung inflammation and infection associated with high rates of mortality. In CF, disrupted ion exchange in the epithelium results in excessive mucus production and reduced mucociliary clearance, leading to immune system exacerbation and chronic infections with pathogens such as P. aeruginosa and S. aureus. It is believed that P. aeruginosa drives gMDSC function as a means of immune evasion, leading to chronic infection. We review the current literature regarding immune suppression in CF by gMDSCs with an emphasis on T cell impairment and the role of P. aeruginosa in this dynamic interaction. Disruption in CFTR function leads to ion dysregulation, abnormal pH, mucus build-up, chronic inflammation, and infection with pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus.

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Conclusion