IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps

• Published in: Journal of allergy and clinical immunology Vol. 143; no. 4; pp. 1416 - 1425.e4
• Main Authors: Lan, Feng, Zhong, Hua, Zhang, Nan, Johnston, Sebastian L., Wen, Weiping, Papadopoulos, Nikos, Zhang, Luo, Bachert, Claus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2019; Elsevier Limited
• Subjects: Adult; antibacterial activity; Antibiotics; Antiviral activity; Bacterial infections; Chronic rhinosinusitis with nasal polyps; Colonization; Female; Humans; IFN-λ1; Immunofluorescence; Infections; Inflammation; Interferon; Interferons - immunology; Interleukins - immunology; Intracellular; Intracellular killing; Janus kinase; LAMP-1 protein; Lymphocytes T; Macrophages; Macrophages - immunology; Male; Membrane proteins; Middle Aged; Mucosa; Nasal Mucosa - immunology; Nasal Mucosa - microbiology; Nasal Polyps - immunology; Nasal Polyps - microbiology; Polyps; Reactive oxygen species; Rhinitis; Rhinitis - immunology; Rhinitis - microbiology; Rhinosinusitis; Signal transduction; Sinusitis; Sinusitis - immunology; Sinusitis - microbiology; Staphylococcal Infections - immunology; Staphylococcus aureus; Transcription; Viral infections; Viruses; antibacterial activity; IFN-λ1; M1; M2; PMA; DAPI; CRSwNP; macrophages; STAT; CFU; Chronic rhinosinusitis with nasal polyps; LAMP1; JAK; IL-28R; MDM; ROS; DPI; Staphylococcus aureus; TCM
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2018.09.041

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by TH2-skewed inflammation and increased colonization by Staphylococcus aureus. IFN-λ1 is known for its antiviral activity, but there is little information on its antibacterial role. We sought to determine the expression and release of IFN-λ1 from nasal mucosal tissue of healthy subjects and patients with CRSwNP on exposure to S aureus and assess its potential role in antibacterial defense mechanisms. Nasal tissue from healthy subjects and patients with CRSwNP was exposed to S aureus, and we assessed expression of IFN-λ1, MUC5AC, and MUC5B. THP1-derived macrophages incubated with or without IFN-λ1 were assessed for uptake and killing of S aureus and expression of lysosomal-associated membrane protein 1 and intracellular reactive oxidase substrate (ROS), the IFN-λ1 receptor IL-28 receptor (IL-28R), and the Janus kinase/signal transducer and activator of transcription (STAT) 1 pathway by means of immunofluorescence staining. S aureus infection increased IFN-λ1 expression in tissue from patients with CRSwNP. IFN-λ1 (10 ng/mL) significantly decreased the number of S aureus colony-forming units in healthy control tissue but not in tissue from patients with CRSwNP and upregulated MUC5AC and MUC5B expression in control tissue on S aureus infection. IFN-λ1 stimulation increased intracellular killing of S aureus in THP1-derived macrophages and substantially increased lysosomal-associated membrane protein 1, IL-28R, ROS, and STAT signaling in macrophages incubated with S aureus. All of these effects were attenuated by blocking IL-28R and ROS activities. IFN-λ1 favors clearance of S aureus in healthy nasal mucosa and enhances antibacterial function of macrophages through IFN-λ1–IL-28R–ROS–Janus kinase–STAT signaling pathways. ▪