Open AccessCF monocyte-derived macrophages have an attenuated response to extracellular vesicles secreted by airway epithelial cells
Author(s) -
Katja Koeppen,
Amanda B. Nymon,
Roxanna Barnaby,
Zhongyou Li,
Thomas H. Hampton,
Alix Ashare,
Bruce A. Stanton
Publication year - 2021
Publication title -
american journal of physiology. lung cellular and molecular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.892
H-Index - 163
eISSN - 1522-1504
pISSN - 1040-0605
DOI - 10.1152/ajplung.00621.2020
Subject(s) - chemokine , innate immune system , immune system , secretion , inflammation , proinflammatory cytokine , macrophage , biology , immunology , monocyte , microbiology and biotechnology , extracellular vesicle , ccl2 , cytokine , cystic fibrosis , microvesicles , in vitro , gene , biochemistry , microrna , genetics
Mutations in CFTR alter macrophage responses, for example, by reducing their ability to phagocytose and kill bacteria. Altered macrophage responses may facilitate bacterial infection and inflammation in the lungs, contributing to morbidity and mortality in cystic fibrosis (CF). Extracellular vesicles (EVs) are secreted by multiple cell types in the lungs and participate in the host immune response to bacterial infection, but the effect of EVs secreted by CF airway epithelial cells (AEC) on CF macrophages is unknown. This report examines the effect of EVs secreted by primary AEC on monocyte-derived macrophages (MDM) and contrasts responses of CF and wild type (WT) MDM. We found that EVs generally increase pro-inflammatory cytokine secretion and expression of innate immune genes in MDM, especially when EVs are derived from AEC exposed to Pseudomonas aeruginosa and that this effect is attenuated in CF MDM. Specifically, EVs secreted by P. aeruginosa exposed AEC (EV-PA) induced immune response genes and increased secretion of proinflammatory cytokines, chemoattractants, and chemokines involved in tissue repair by WT MDM, but these effects were less robust in CF MDM. We attribute attenuated responses by CF MDM to differences between CF and WT macrophages because EVs secreted by CF AEC or WT AEC elicited similar responses in CF MDM. Our findings demonstrate the importance of AEC EVs in macrophage responses and show that the Phe508del mutation in CFTR attenuates the innate immune response of MDM to EVs.