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CF monocyte-derived macrophages have an attenuated response to extracellular vesicles secreted by airway epithelial cells.
Koeppen, Katja; Nymon, Amanda; Barnaby, Roxanna; Li, Zhongyou; Hampton, Thomas H; Ashare, Alix; Stanton, Bruce A.
Afiliação
  • Koeppen K; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
  • Nymon A; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
  • Barnaby R; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
  • Li Z; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
  • Hampton TH; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
  • Ashare A; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
  • Stanton BA; Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
Am J Physiol Lung Cell Mol Physiol ; 320(4): L530-L544, 2021 04 01.
Article em En | MEDLINE | ID: mdl-33471607
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Pseudomonas / Fibrose Cística / Vesículas Extracelulares / Imunidade Inata / Inflamação / Pulmão / Macrófagos Limite: Humans Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Assunto da revista: BIOLOGIA MOLECULAR / FISIOLOGIA Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Pseudomonas / Fibrose Cística / Vesículas Extracelulares / Imunidade Inata / Inflamação / Pulmão / Macrófagos Limite: Humans Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Assunto da revista: BIOLOGIA MOLECULAR / FISIOLOGIA Ano de publicação: 2021 Tipo de documento: Article