Cystic Fibrosis Lung Transplant Recipients Have Suppressed Airway Interferon Responses during Pseudomonas Infection

Daniel T. Dugger; Monica Fung; Lorna Zlock; Saharai Caldera; Louis Sharp; Steven R. Hays; Jonathan P. Singer; Lorriana E. Leard; Jefferey A. Golden; Rupal J. Shah; Jasleen Kukreja; Erin Gordon; Walter Finkbeiner; Mary Ellen Kleinhenz; Chaz Langelier; John R. Greenland

Cell Reports Medicine (Jul 2020)

Cystic Fibrosis Lung Transplant Recipients Have Suppressed Airway Interferon Responses during Pseudomonas Infection

Daniel T. Dugger,
Monica Fung,
Lorna Zlock,
Saharai Caldera,
Louis Sharp,
Steven R. Hays,
Jonathan P. Singer,
Lorriana E. Leard,
Jefferey A. Golden,
Rupal J. Shah,
Jasleen Kukreja,
Erin Gordon,
Walter Finkbeiner,
Mary Ellen Kleinhenz,
Chaz Langelier,
John R. Greenland

Affiliations

Daniel T. Dugger: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Monica Fung: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Lorna Zlock: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA
Saharai Caldera: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Louis Sharp: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Steven R. Hays: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Jonathan P. Singer: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Lorriana E. Leard: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Jefferey A. Golden: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Rupal J. Shah: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Jasleen Kukreja: Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA
Erin Gordon: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Walter Finkbeiner: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA
Mary Ellen Kleinhenz: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Chaz Langelier: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub, San Francisco, CA 94143, USA
John R. Greenland: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Medical Service, Veterans Affairs Health Care System, San Francisco, CA 94121, USA; Corresponding author

Journal volume & issue: Vol. 1, no. 4
p. 100055

Abstract

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Summary: Lung transplantation can be lifesaving in end-stage cystic fibrosis (CF), but long-term survival is limited by chronic lung allograft dysfunction (CLAD). Persistent upper airway Pseudomonas aeruginosa (PsA) colonization can seed the allograft. While de novo PsA infection is associated with CLAD in non-CF recipients, this association is less clear for CF recipients experiencing PsA recolonization. Here, we evaluate host and pathogen contributions to this phenomenon. In the context of PsA infection, brushings from the airways of CF recipients demonstrate type 1 interferon gene suppression. Airway epithelial cell (AEC) cultures demonstrate similar findings in the absence of pathogens or immune cells, contrasting with the pre-transplant CF AEC phenotype. Type 1 interferon promoters are relatively hypermethylated in CF AECs. CF subjects in this cohort have more mucoid PsA, while non-CF PsA subjects have decreased microbiome α diversity. Peri-transplant protocols may benefit from consideration of this host and microbiome equilibrium.

Published in Cell Reports Medicine

ISSN: 2666-3791 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General)
Website: https://www.cell.com/cell-reports-medicine

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