title: The emerging potential of autophagy-based therapies in the treatment of cystic fibrosis lung infections.
abstract: Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), a channel that normally transports anions across epithelial cell membranes. The most common manifestation of CF is buildup of mucus in the airways and bacterial colonization of the lower respiratory tract, accompanied by chronic inflammation. Antibiotics are used to control CF-associated opportunistic infections, but lengthy antibiotic treatment risks the emergence of multiple-drug resistant (MDR) strains. New antimicrobial strategies are needed to prevent and treat infections in these high-risk individuals. Autophagy contributes to the control of a variety of microbial infections. For this reason, the recent discovery of functional impairment of autophagy in CF provides a new basis for understanding susceptibility to severe infections. Here, we review the role of autophagy in host defense against CF-associated bacterial and fungal pathogens, and survey pharmacologic approaches to restore normal autophagy function in these individuals. Autophagy restoration therapy may improve pathogen clearance and mitigate lung inflammation in CF airways.
authors.affiliation: Department of Microbiology and Immunology; Dalhousie University; Halifax, NS CA; Department of Pediatrics; IWK Health Centre; Halifax, NS CA; Beatrice Hunter Cancer Research Institute; Halifax, NS CA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Junkins
authors.affiliation: Department of Microbiology and Immunology; Dalhousie University; Halifax, NS CA; Beatrice Hunter Cancer Research Institute; Halifax, NS CA.
authors.forename: Craig
authors.initials: C
authors.lastname: McCormick
authors.affiliation: Department of Microbiology and Immunology; Dalhousie University; Halifax, NS CA; Department of Pediatrics; IWK Health Centre; Halifax, NS CA; Beatrice Hunter Cancer Research Institute; Halifax, NS CA.
authors.forename: Tong-Jun
authors.initials: TJ
authors.lastname: Lin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D006801:Humans; D008407:Mast Cells / Q000502:physiology*; D018410:Pneumonia, Bacterial / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*
keywords: A. fumigatus; B. cepacia; BECN1; H. influenza; P. aeruginosa; S. aureus; TGM2; autophagy; cystic fibrosis; non-tuberculosis mycobacterium; rapamycin