COPD; IL-20 cytokines; cigarette; lung; viral infection; Medicine (miscellaneous); Biochemistry, Genetics and Molecular Biology (all); General Biochemistry, Genetics and Molecular Biology
Abstract :
[en] (1) Background: viral infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are responsible for disease progression and mortality. Previous reports showed that IL-20 cytokines facilitate bacterial lung infection, but their production and their role in COPD and viral infection has not yet been investigated. (2) Methods: C57BL/6 WT and IL-20 Rb KO mice were chronically exposed to air or cigarette smoke (CS) to mimic COPD. Cytokine production, antiviral response, inflammation and tissue damages were analyzed after PVM infection. (3) Results: CS exposure was associated with an increase in viral burden and antiviral response. PVM infection in CS mice enhanced IFN-γ, inflammation and tissue damage compared to Air mice. PVM infection and CS exposure induced, in an additive manner, IL-20 cytokines expression and the deletion of IL-20 Rb subunit decreased the expression of interferon-stimulated genes and the production of IFN-λ2/3, without an impact on PVM replication. Epithelial cell damages and inflammation were also reduced in IL-20 Rb-/- mice, and this was associated with reduced lung permeability and the maintenance of intercellular junctions. (4) Conclusions: PVM infection and CS exposure additively upregulates the IL-20 pathway, leading to the promotion of epithelial damages. Our data in our model of viral exacerbation of COPD identify IL-20 cytokine as a potential therapeutic target.
Disciplines :
Microbiology
Author, co-author :
Le Roux, Mélina; CIIL-Center for Infection and Immunity of Lille, CHRU Lille, Institute Pasteur de Lille, University Lille, CNRS UMR9017, Inserm U1019, 59000 Lille, France
Ollivier, Anaïs ; CIIL-Center for Infection and Immunity of Lille, CHRU Lille, Institute Pasteur de Lille, University Lille, CNRS UMR9017, Inserm U1019, 59000 Lille, France
Kervoaze, Gwenola; CIIL-Center for Infection and Immunity of Lille, CHRU Lille, Institute Pasteur de Lille, University Lille, CNRS UMR9017, Inserm U1019, 59000 Lille, France
Beke, Timothé; CIIL-Center for Infection and Immunity of Lille, CHRU Lille, Institute Pasteur de Lille, University Lille, CNRS UMR9017, Inserm U1019, 59000 Lille, France
Gillet, Laurent ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Pichavant, Muriel; CIIL-Center for Infection and Immunity of Lille, CHRU Lille, Institute Pasteur de Lille, University Lille, CNRS UMR9017, Inserm U1019, 59000 Lille, France
Gosset, Philippe ; CIIL-Center for Infection and Immunity of Lille, CHRU Lille, Institute Pasteur de Lille, University Lille, CNRS UMR9017, Inserm U1019, 59000 Lille, France
Language :
English
Title :
IL-20 Cytokines Are Involved in Epithelial Lesions Associated with Virus-Induced COPD Exacerbation in Mice.
Région Hauts-de-France [FR] CNRS - French National Centre for Scientific Research [FR] INSERM - French Institute of Health and Medical Research [FR] ULille - University of Lille [FR] Fondation du Souffle [FR]
Funding text :
Funding: This research received no external funding. This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Lille (Lille, France) and the Region Hauts de France and Fondation de Recherche en Santé Respiratoire (Paris, France). Funders had no role in study design, data collection, data analysis, interpretation or writing of the report.
Guo-Parke, H.; Linden, D.; Weldon, S.; Kidney, J.C.; Taggart, C.C. Mechanisms of Virus-Induced Airway Immunity Dysfunction in the Pathogenesis of COPD Disease, Progression, and Exacerbation. Front. Immunol. 2020, 11. [CrossRef]
Soler-Cataluña, J.J.; Martínez-García, M.Á.; Sánchez, P.R.; Salcedo, E.; Navarro, M.; Ochando, R. Yy. Thorax 2005, 60, 925–931. [CrossRef]
Majzoub, K.; Wrensch, F.; Baumert, T.F. The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans. Viruses 2019, 11, 758. [CrossRef]
Egli, A.; Santer, D.M.; O’Shea, D.; Tyrrell, D.L.; Houghton, M. The Impact of the Interferon-Lambda Family on the Innate and Adaptive Immune Response to Viral Infections. Emerg. Microbes Infect. 2014, 3, 1–12. [CrossRef] [PubMed]
Okabayashi, T.; Kojima, T.; Masaki, T.; Yokota, S.; Imaizumi, T.; Tsutsumi, H.; Himi, T.; Fujii, N.; Sawada, N. Type-III Interferon, Not Type-I, Is the Predominant Interferon Induced by Respiratory Viruses in Nasal Epithelial Cells. Virus Res. 2011, 160, 360–366. [CrossRef]
Kumar, P.; Thakar, M.S.; Ouyang, W.; Malarkannan, S. IL-22 from Conventional NK Cells Is Epithelial Regenerative and Inflammation Protective during Influenza Infection. Mucosal Immunol. 2013, 6, 69–82. [CrossRef]
Barthelemy, A.; Sencio, V.; Soulard, D.; Deruyter, L.; Faveeuw, C.; Le Goffic, R.; Trottein, F. Interleukin-22 Immunotherapy during Severe Influenza Enhances Lung Tissue Integrity and Reduces Secondary Bacterial Systemic Invasion. Infect. Immun. 2018, 86. [CrossRef]
Koné, B.; Pérez-Cruz, M.; Porte, R.; Hennegrave, F.; Carnoy, C.; Gosset, P.; Trottein, F.; Sirard, J.-C.; Pichavant, M.; Gosset, P. Boosting the IL-22 Response Using Flagellin Prevents Bacterial Infection in Cigarette Smoke-Exposed Mice. Clin. Exp. Immunol. 2020, 201, 171–186. [CrossRef]
Rutz, S.; Wang, X.; Ouyang, W. The IL-20 Subfamily of Cytokines–from Host Defence to Tissue Homeostasis. Nat. Rev. Immunol. 2014, 14, 783–795. [CrossRef]
Madouri, F.; Barada, O.; Kervoaze, G.; Trottein, F.; Pichavant, M.; Gosset, P. Production of Interleukin-20 Cytokines Limits Bacterial Clearance and Lung Inflammation during Infection by Streptococcus Pneumoniae. EBioMedicine 2018, 37, 417–427. [CrossRef]
Myles, I.A.; Fontecilla, N.M.; Valdez, P.A.; Vithayathil, P.J.; Naik, S.; Belkaid, Y.; Ouyang, W.; Datta, S.K. Signaling via the IL-20 Receptor Inhibits Cutaneous Production of IL-1β and IL-17A to Promote Infection with Methicillin-Resistant Staphylococcus Aureus. Nat. Immunol. 2013, 14, 804–811. [CrossRef]
Rong, B.; Liu, Y.; Li, M.; Fu, T.; Gao, W.; Liu, H. Correlation of Serum Levels of HIF-1α and IL-19 with the Disease Progression of COPD: A Retrospective Study. Int. J. Chron. Obstruct. Pulmon. Dis. 2018, 13, 3791–3803. [CrossRef] [PubMed]
Ermers, M.J.J.; Janssen, R.; Onland-Moret, N.C.; Hodemaekers, H.M.; Rovers, M.M.; Houben, M.L.; Kimpen, J.L.L.; Bont, L.J. IL10 Family Member Genes IL19 and IL20 Are Associated with Recurrent Wheeze after Respiratory Syncytial Virus Bronchiolitis. Pediatr. Res. 2011, 70, 518–523. [CrossRef]
Truelove, A.L.; Oleksyk, T.K.; Shrestha, S.; Thio, C.L.; Goedert, J.J.; Donfield, S.M.; Kirk, G.D.; Thomas, D.L.; O’Brien, S.J.; Smith, M.W. Evaluation of IL10, IL19 and IL20 Gene Polymorphisms and Chronic Hepatitis B Infection Outcome. Int. J. Immunogenet. 2008, 35, 255–264. [CrossRef]
Rosenberg, H.F.; Domachowske, J.B. Pneumonia Virus of Mice: Severe Respiratory Infection in a Natural Host. Immunol. Lett. 2008, 118, 6–12. [CrossRef] [PubMed]
Rosenberg, H.F.; Bonville, C.A.; Easton, A.J.; Domachowske, J.B. The Pneumonia Virus of Mice Infection Model for Severe Respiratory Syncytial Virus Infection: Identifying Novel Targets for Therapeutic Intervention. Pharmacol. Ther. 2005, 105, 1–6. [CrossRef] [PubMed]
Pichavant, M.; Rémy, G.; Bekaert, S.; Le Rouzic, O.; Kervoaze, G.; Vilain, E.; Just, N.; Tillie-Leblond, I.; Trottein, F.; Cataldo, D.; et al. Oxidative Stress-Mediated INKT-Cell Activation Is Involved in COPD Pathogenesis. Mucosal Immunol. 2014, 7, 568–578. [CrossRef] [PubMed]
Sharan, R.; Perez-Cruz, M.; Kervoaze, G.; Gosset, P.; Weynants, V.; Godfroid, F.; Hermand, P.; Trottein, F.; Pichavant, M.; Gosset, P. Interleukin-22 Protects against Non-Typeable Haemophilus Influenzae Infection: Alteration during Chronic Obstructive Pulmonary Disease. Mucosal Immunol. 2017, 10, 139–149. [CrossRef]
Bosteels, C.; Neyt, K.; Vanheerswynghels, M.; van Helden, M.J.; Sichien, D.; Debeuf, N.; De Prijck, S.; Bosteels, V.; Vandamme, N.; Martens, L.; et al. Inflammatory Type 2 CDCs Acquire Features of CDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection. Immunity 2020, 52, 1039–1056.e9. [CrossRef]
Hogea, S.-P.; Tudorache, E.; Fildan, A.P.; Fira-Mladinescu, O.; Marc, M.; Oancea, C. Risk Factors of Chronic Obstructive Pulmonary Disease Exacerbations. Clin. Respir. J. 2020, 14, 183–197. [CrossRef] [PubMed]
MOHAN, A.; CHANDRA, S.; AGARWAL, D.; GULERIA, R.; BROOR, S.; GAUR, B.; PANDEY, R.M. Prevalence of Viral Infection Detected by PCR and RT-PCR in Patients with Acute Exacerbation of COPD: A Systematic Review. Respirol. Carlton Vic 2010, 15, 536–542. [CrossRef] [PubMed]
Rohde, G.; Wiethege, A.; Borg, I.; Kauth, M.; Bauer, T.T.; Gillissen, A.; Bufe, A.; Schultze-Werninghaus, G. Respiratory Viruses in Exacerbations of Chronic Obstructive Pulmonary Disease Requiring Hospitalisation: A Case-Control Study. Thorax 2003, 58, 37–42. [CrossRef]
Wilkinson, T.M.A.; Donaldson, G.C.; Johnston, S.L.; Openshaw, P.J.M.; Wedzicha, J.A. Respiratory Syncytial Virus, Airway Inflammation, and FEV1 Decline in Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2006, 173, 871–876. [CrossRef] [PubMed]
Randall, R.E.; Goodbourn, S. Interferons and Viruses: An Interplay between Induction, Signalling, Antiviral Responses and Virus Countermeasures. J. Gen. Virol. 2008, 89, 1–47. [CrossRef]
Singanayagam, A.; Loo, S.-L.; Calderazzo, M.; Finney, L.J.; Trujillo Torralbo, M.-B.; Bakhsoliani, E.; Girkin, J.; Veerati, P.; Pathinayake, P.S.; Nichol, K.S.; et al. Antiviral Immunity Is Impaired in COPD Patients with Frequent Exacerbations. Am. J. Physiol.-Lung Cell. Mol. Physiol. 2019, 317, L893–L903. [CrossRef]
García-Valero, J.; Olloquequi, J.; Montes, J.F.; Rodríguez, E.; Martín-Satué, M.; Texidó, L.; Ferrer Sancho, J. Deficient Pulmonary IFN-β Expression in COPD Patients. PLoS ONE 2019, 14, e0217803. [CrossRef]
Hsu, A.C.-Y.; Dua, K.; Starkey, M.R.; Haw, T.-J.; Nair, P.M.; Nichol, K.; Zammit, N.; Grey, S.T.; Baines, K.J.; Foster, P.S.; et al. MicroRNA-125a and-b Inhibit A20 and MAVS to Promote Inflammation and Impair Antiviral Response in COPD. JCI Insight 2017, 2, e90443. [CrossRef]
Wu, W.; Patel, K.B.; Booth, J.L.; Zhang, W.; Metcalf, J.P. Cigarette Smoke Extract Suppresses the RIG-I-Initiated Innate Immune Response to Influenza Virus in the Human Lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 2011, 300, L821–L830. [CrossRef]
Hilzendeger, C.; da Silva, J.; Henket, M.; Schleich, F.; Corhay, J.L.; Kebadze, T.; Edwards, M.R.; Mallia, P.; Johnston, S.L.; Louis, R. Reduced Sputum Expression of Interferon-Stimulated Genes in Severe COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 2016, 11, 1485–1494. [CrossRef]
Baines, K.J.; Hsu, A.C.-Y.; Tooze, M.; Gunawardhana, L.P.; Gibson, P.G.; Wark, P.A. Novel Immune Genes Associated with Excessive Inflammatory and Antiviral Responses to Rhinovirus in COPD. Respir. Res. 2013, 14, 15. [CrossRef] [PubMed]
Collinson, N.; Snape, N.; Beagley, K.; Fantino, E.; Spann, K. COPD Is Associated with Elevated IFN-β Production by Bronchial Epithelial Cells Infected with RSV or HMPV. Viruses 2021, 13, 911. [CrossRef] [PubMed]
Foronjy, R.F.; Dabo, A.J.; Taggart, C.C.; Weldon, S.; Geraghty, P. Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice. PLoS ONE 2014, 9, e90567. [CrossRef]
Watkiss, E.R.T.; Shrivastava, P.; Arsic, N.; Gomis, S.; Van Drunen Littel-van den Hurk, S. Innate and Adaptive Immune Response to Pneumonia Virus of Mice in a Resistant and a Susceptible Mouse Strain. Viruses 2013, 5, 295–320. [CrossRef]
Van Helden, M.J.G.; van Kooten, P.J.S.; Bekker, C.P.J.; Gröne, A.; Topham, D.J.; Easton, A.J.; Boog, C.J.P.; Busch, D.H.; Zaiss, D.M.W.; Sijts, A.J.A.M. Pre-Existing Virus-Specific CD8+ T-Cells Provide Protection against Pneumovirus-Induced Disease in Mice. Vaccine 2012, 30, 6382–6388. [CrossRef]
Van Leuven, J.T.; Gonzalez, A.J.; Ijezie, E.C.; Wixom, A.Q.; Clary, J.L.; Naranjo, M.N.; Ridenhour, B.J.; Miller, C.R.; Miura, T.A. Rhinovirus Reduces the Severity of Subsequent Respiratory Viral Infections by Interferon-Dependent and-Independent Mechanisms. mSphere 2021, 6, e0047921. [CrossRef]
Seong, R.-K.; Choi, Y.-K.; Shin, O.S. MDA7/IL-24 Is an Anti-Viral Factor That Inhibits Influenza Virus Replication. J. Microbiol. Seoul Korea 2016, 54, 695–700. [CrossRef]
Strumillo, S.T.; Curcio, M.F.; de Carvalho, F.F., Jr.; Sucupira, M.A.; Diaz, R.S.; Monteiro, H.P.; Janini, L.M.R. HIV-1 Infection Modulates IL-24 Expression Which Contributes to Cell Apoptosis in Vitro. Cell Biol. Int. 2019, 43, 574–579. [CrossRef] [PubMed]
Hsu, Y.-H.; Wu, C.-Y.; Hsing, C.-H.; Lai, W.-T.; Wu, L.-W.; Chang, M.-S. Anti-IL-20 Monoclonal Antibody Suppresses Prostate Cancer Growth and Bone Osteolysis in Murine Models. PLoS ONE 2015, 10, e0139871. [CrossRef]
Nakada, T.-A.; Wacharasint, P.; Russell, J.A.; Boyd, J.H.; Nakada, E.; Thair, S.A.; Shimada, T.; Walley, K.R. The IL20 Genetic Polymorphism Is Associated with Altered Clinical Outcome in Septic Shock. J. Innate Immun. 2018, 10, 181–188. [CrossRef] [PubMed]
