The SPLUNC1-βENaC complex prevents Burkholderia cenocepacia invasion in normal airway epithelia

• Published in: Respiratory research Vol. 21; no. 1; pp. 190 - 9
• Main Authors: Ahmad, Saira, Kim, Christine Seul Ki, Tarran, Robert
• Format: Journal Article
• Language: English
• Published: England BioMed Central 17.07.2020; BMC
• Subjects: Adolescent; Adult; Animals; Antimicrobial agents; Bacterial infections; Bacterial Load; BPIFA1; Burkholderia cenocepacia - pathogenicity; Burkholderia Infections - genetics; Burkholderia Infections - metabolism; Burkholderia Infections - microbiology; Case-Control Studies; CFTR; Cystic fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis - metabolism; Cystic Fibrosis - microbiology; Disease Models, Animal; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Epithelial Sodium Channels - genetics; Epithelial Sodium Channels - metabolism; Etiology; Female; Glycoproteins - genetics; Glycoproteins - metabolism; HEK293 Cells; Host-Pathogen Interactions; Humans; Infections; Innate defense; Lung - metabolism; Lung - microbiology; Lungs; Male; Membranes; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Palate; Phosphoproteins - genetics; Phosphoproteins - metabolism; Physiology; Respiratory Tract Infections - genetics; Respiratory Tract Infections - metabolism; Respiratory Tract Infections - microbiology; Software; Transplants & implants; Young Adult; pH; Cystic fibrosis; BPIFA1; Innate defense; CFTR
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-020-01454-5

Cystic fibrosis (CF) patients are extremely vulnerable to Burkholderia cepacia complex (Bcc) infections. However, the underlying etiology is poorly understood. We tested the hypothesis that short palate lung and nasal epithelial clone 1 (SPLUNC1)-epithelial sodium channel (ENaC) interactions at the plasma membrane are required to reduce Bcc burden in normal airways. To determine if SPLUNC1 was needed to reduce Bcc burden in the airways, SPLUNC1 knockout mice and their wild-type littermates were infected with B. cenocepacia strain J2315. SPLUNC1 knockout mice had increased bacterial burden in the lungs compared to wild-type littermate mice. SPLUNC1-knockdown primary human bronchial epithelia (HBECs) were incubated with J2315, which resulted in increased bacterial burden compared to non-transduced HBECs. We next determined the interaction of the SPLUNC1-ENaC complex during J2315 infection. SPLUNC1 remained at the apical plasma membrane of normal HBECs but less was present at the apical plasma membrane of CF HBECs. Additionally, SPLUNC1-βENaC complexes reduced intracellular J2315 burden. Our data indicate that (i) secreted SPLUNC1 is required to reduce J2315 burden in the airways and (ii) its interaction with ENaC prevents cellular invasion of J2315.