IFNλ: Balancing the Light and Dark Side in Pulmonary Infection

Overview

Journal mBio

Publisher American Society for Microbiology

Specialty Microbiology

Date 2023 Jun 6

PMID 37278532

Authors

Danielle Antos

John F Alcorn

Affiliations

Soon will be listed here.

Abstract

Interferon (IFN) represents a well-known component of antiviral immunity that has been studied extensively for its mechanisms of action and therapeutic potential when antiviral treatment options are limited. Specifically in the respiratory tract, IFNs are induced directly on viral recognition to limit the spread and transmission of the virus. Recent focus has been on the IFNλ family, which has become an exciting focus in recent years for its potent antiviral and anti-inflammatory activities against viruses infecting barrier sites, including the respiratory tract. However, insights into the interplay between IFNλs and other pulmonary infections are more limited and suggest a more complex role, potentially detrimental, than what was seen during viral infections. Here, we review the role of IFNλs in pulmonary infections, including viral, bacterial, fungal, and multi-pathogen super-infections, and how this may impact future work in the field.

Citing Articles

Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection.

Mihaescu G, Chifiriuc M, Filip R, Bleotu C, Ditu L, Constantin M Front Immunol. 2024; 14:1273604.

PMID: 38288121 PMC: 10822962. DOI: 10.3389/fimmu.2023.1273604.

Advances in preparation and application of antibacterial hydrogels.

Tang Y, Xu H, Wang X, Dong S, Guo L, Zhang S J Nanobiotechnology. 2023; 21(1):300.

PMID: 37633883 PMC: 10463510. DOI: 10.1186/s12951-023-02025-8.

References

Bolen C, Ding S, Robek M, Kleinstein S . Dynamic expression profiling of type I and type III interferon-stimulated hepatocytes reveals a stable hierarchy of gene expression. Hepatology. 2013; 59(4):1262-72. PMC: 3938553. DOI: 10.1002/hep.26657. View

Klinkhammer J, Schnepf D, Ye L, Schwaderlapp M, Gad H, Hartmann R . IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission. Elife. 2018; 7. PMC: 5953542. DOI: 10.7554/eLife.33354. View

Crotta S, Davidson S, Mahlakoiv T, Desmet C, Buckwalter M, Albert M . Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia. PLoS Pathog. 2013; 9(11):e1003773. PMC: 3836735. DOI: 10.1371/journal.ppat.1003773. View

Ahn D, Prince A . Participation of the IL-10RB Related Cytokines, IL-22 and IFN-λ in Defense of the Airway Mucosal Barrier. Front Cell Infect Microbiol. 2020; 10:300. PMC: 7318800. DOI: 10.3389/fcimb.2020.00300. View

Sharma L, Peng X, Qing H, Hilliard B, Kim J, Swaminathan A . Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection. J Virol. 2021; 96(2):e0124121. PMC: 8791255. DOI: 10.1128/JVI.01241-21. View

Santer D, Li D, Ghosheh Y, Zahoor M, Prajapati D, Hansen B . Interferon-λ treatment accelerates SARS-CoV-2 clearance despite age-related delays in the induction of T cell immunity. Nat Commun. 2022; 13(1):6992. PMC: 9667439. DOI: 10.1038/s41467-022-34709-4. View

Medaglia C, Zwygart A, Silva P, Constant S, Huang S, Stellacci F . Interferon Lambda Delays the Emergence of Influenza Virus Resistance to Oseltamivir. Microorganisms. 2021; 9(6). PMC: 8227012. DOI: 10.3390/microorganisms9061196. View

Rich H, McCourt C, Zheng W, McHugh K, Robinson K, Wang J . Interferon Lambda Inhibits Bacterial Uptake during Influenza Superinfection. Infect Immun. 2019; 87(5). PMC: 6479047. DOI: 10.1128/IAI.00114-19. View

Chattoraj S, Ganesan S, Faris A, Comstock A, Lee W, Sajjan U . Pseudomonas aeruginosa suppresses interferon response to rhinovirus infection in cystic fibrosis but not in normal bronchial epithelial cells. Infect Immun. 2011; 79(10):4131-45. PMC: 3187241. DOI: 10.1128/IAI.05120-11. View

10.

Robinson K, Kolls J, Alcorn J . The immunology of influenza virus-associated bacterial pneumonia. Curr Opin Immunol. 2015; 34:59-67. PMC: 4444379. DOI: 10.1016/j.coi.2015.02.002. View

11.

Lebreton A, Lakisic G, Job V, Fritsch L, Tham T, Camejo A . A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response. Science. 2011; 331(6022):1319-21. DOI: 10.1126/science.1200120. View

12.

Munoz-Moreno R, Martinez-Romero C, Garcia-Sastre A . Induction and Evasion of Type-I Interferon Responses during Influenza A Virus Infection. Cold Spring Harb Perspect Med. 2020; 11(10). PMC: 8485741. DOI: 10.1101/cshperspect.a038414. View

13.

Morgan D, Casulli J, Chew C, Connolly E, Lui S, Brand O . Innate Immune Cell Suppression and the Link With Secondary Lung Bacterial Pneumonia. Front Immunol. 2019; 9:2943. PMC: 6302086. DOI: 10.3389/fimmu.2018.02943. View

14.

Pierangeli A, Statzu M, Nenna R, Santinelli L, Petrarca L, Frassanito A . Interferon lambda receptor 1 (IFNL1R) transcript is highly expressed in rhinovirus bronchiolitis and correlates with disease severity. J Clin Virol. 2018; 102:101-109. DOI: 10.1016/j.jcv.2018.03.003. View

15.

Lan F, Zhong H, Zhang N, Johnston S, Wen W, Papadopoulos N . IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps. J Allergy Clin Immunol. 2018; 143(4):1416-1425.e4. DOI: 10.1016/j.jaci.2018.09.041. View

16.

Yin Z, Dai J, Deng J, Sheikh F, Natalia M, Shih T . Type III IFNs are produced by and stimulate human plasmacytoid dendritic cells. J Immunol. 2012; 189(6):2735-45. PMC: 3579503. DOI: 10.4049/jimmunol.1102038. View

17.

Miknis Z, Magracheva E, Li W, Zdanov A, Kotenko S, Wlodawer A . Crystal structure of human interferon-λ1 in complex with its high-affinity receptor interferon-λR1. J Mol Biol. 2010; 404(4):650-64. PMC: 2991516. DOI: 10.1016/j.jmb.2010.09.068. View

18.

Espinosa V, Dutta O, McElrath C, Du P, Chang Y, Cicciarelli B . Type III interferon is a critical regulator of innate antifungal immunity. Sci Immunol. 2017; 2(16). PMC: 5880030. DOI: 10.1126/sciimmunol.aan5357. View

19.

Pietila T, Latvala S, Osterlund P, Julkunen I . Inhibition of dynamin-dependent endocytosis interferes with type III IFN expression in bacteria-infected human monocyte-derived DCs. J Leukoc Biol. 2010; 88(4):665-74. DOI: 10.1189/jlb.1009651. View

20.

Beucher G, Blondot M, Celle A, Pied N, Recordon-Pinson P, Esteves P . Bronchial epithelia from adults and children: SARS-CoV-2 spread via syncytia formation and type III interferon infectivity restriction. Proc Natl Acad Sci U S A. 2022; 119(28):e2202370119. PMC: 9651868. DOI: 10.1073/pnas.2202370119. View