Interferon Lambda Inhibits Bacterial Uptake during Influenza Superinfection

• Published in: Infection and immunity 2019-05, Vol.87 (5)
• Main Authors: Rich, Helen E, McCourt, Collin C, Zheng, Wen Quan, McHugh, Kevin J, Robinson, Keven M, Wang, Jieru, Alcorn, John F
• Format: Article
• Language: English
• Subjects: Animals; Antiviral Agents - therapeutic use; Disease Models, Animal; Disease Susceptibility; Host Response and Inflammation; Humans; Influenza, Human - complications; Influenza, Human - drug therapy; Interferons - therapeutic use; Male; Mice; Mice, Inbred C57BL; Staphylococcal Infections - pathology; Staphylococcus aureus - drug effects; Streptococcus pneumoniae - drug effects; Superinfection - drug therapy; Superinfection - etiology; United States
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00114-19

Influenza kills 30,000 to 40,000 people each year in the United States and causes 10 times as many hospitalizations. A common complication of influenza is bacterial superinfection, which exacerbates morbidity and mortality from the viral illness. Recently, methicillin-resistant (MRSA) has emerged as the dominant pathogen found in bacterial superinfection, with a close second. However, clinicians have few tools to treat bacterial superinfection. Current therapy for influenza/bacterial superinfection consists of treating the underlying influenza infection and adding various antibiotics, which are increasingly rendered ineffective by rising bacterial multidrug resistance. Several groups have recently proposed the use of the antiviral cytokine interferon lambda (IFN-λ) as a therapeutic for influenza, as administration of pegylated IFN-λ improves lung function and survival during influenza by reducing the overabundance of neutrophils in the lung. However, our data suggest that therapeutic IFN-λ impairs bacterial clearance during influenza superinfection. Specifically, mice treated with an adenoviral vector to overexpress IFN-λ during influenza infection exhibited increased bacterial burdens upon superinfection with either MRSA or Surprisingly, adhesion molecule expression, antimicrobial peptide production, and reactive oxygen species activity were not altered by IFN-λ treatment. However, neutrophil uptake of MRSA and was significantly reduced upon IFN-λ treatment during influenza superinfection Together, these data support the theory that IFN-λ decreases neutrophil motility and function in the influenza-infected lung, which increases the bacterial burden during superinfection. Thus, we believe that caution should be exercised in the possible future use of IFN-λ as therapy for influenza.