{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:48:33Z","timestamp":1791244113269,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:00:00Z","timestamp":1734739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["1122506"],"award-info":[{"award-number":["1122506"]}]},{"name":"National Health and Medical Research Council of Australia","award":["1128276"],"award-info":[{"award-number":["1128276"]}]},{"name":"National Health and Medical Research Council of Australia","award":["2002948"],"award-info":[{"award-number":["2002948"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Severe lower respiratory tract disease following influenza A virus (IAV) infection is characterized by excessive inflammation and lung tissue damage, and this can impair lung function. The effect of toll-like receptor 7 (TLR7), which detects viral RNA to initiate antiviral and proinflammatory responses to IAV, on lung function during peak infection and in the resolution phase is not fully understood. Using wild-type (WT) C57BL\/6 and TLR7 knockout (TLR7 KO) mice, we found that IAV infection induced airway dysfunction in both genotypes, although in TLR7 KO mice, this dysfunction manifested later, did not affect lung tissue elastance and damping, and was associated with a different immune phenotype. A positive correlation was found between lung dysfunction and the infiltration of neutrophils and Ly6Clo patrolling monocytes at day 7 post-infection. Conversely, in TLR7 KO mice, eosinophil and CD8+ cytotoxic T cells were associated with airway hyperactivity at day 14. IL-5 expression was higher in the airways of IAV-infected TLR7 KO mice, suggesting an enhanced Th2 response due to TLR7 deficiency. This study highlights an underappreciated duality of TLR7 in IAV disease: promoting inflammation-driven lung dysfunction during the acute infection but suppressing eosinophilic and CD8+ T cell-dependent hyperresponsiveness during disease resolution.<\/jats:p>","DOI":"10.3390\/ijms252413699","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T04:33:29Z","timestamp":1734928409000},"page":"13699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["TLR7 Promotes Acute Inflammatory-Driven Lung Dysfunction in Influenza-Infected Mice but Prevents Late Airway Hyperresponsiveness"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2162-2939","authenticated-orcid":false,"given":"Mark A.","family":"Miles","sequence":"first","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-858X","authenticated-orcid":false,"given":"Stella","family":"Liong","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Liong","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma S.","family":"Trollope","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0901-5183","authenticated-orcid":false,"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Bozinovski","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7311-9326","authenticated-orcid":false,"given":"John J.","family":"O\u2019Leary","sequence":"additional","affiliation":[{"name":"Discipline of Histopathology, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, D08 XW7X Dublin, Ireland"},{"name":"Sir Patrick Dun\u2019s Laboratory, Central Pathology Laboratory, St James\u2019s Hospital, D08 XW7X Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9098-3626","authenticated-orcid":false,"given":"Doug A.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-7615","authenticated-orcid":false,"given":"Stavros","family":"Selemidis","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2","article-title":"Estimates of global seasonal influenza-associated respiratory mortality: A modelling study","volume":"391","author":"Iuliano","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-018-0002-y","article-title":"Influenza","volume":"4","author":"Krammer","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1093\/cid\/ciq012","article-title":"Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009\u2013April 2010)","volume":"52","author":"Shrestha","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.4049\/jimmunol.2100294","article-title":"Comprehensive Immunologic Evaluation of Bronchoalveolar Lavage Samples from Human Patients with Moderate and Severe Seasonal Influenza and Severe COVID-19","volume":"207","author":"Reynolds","year":"2021","journal-title":"J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"eabe3024","DOI":"10.1126\/sciadv.abe3024","article-title":"Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm","volume":"6","author":"Mudd","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.ajpath.2013.06.023","article-title":"Cytokine and chemokine profiles in lung tissues from fatal cases of 2009 pandemic influenza A (H1N1): Role of the host immune response in pathogenesis","volume":"183","author":"Gao","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ferreira, A.C., Sacramento, C.Q., Pereira-Dutra, F.S., Fintelman-Rodrigues, N., Silva, P.P., Mattos, M., de Freitas, C.S., Marttorelli, A., de Melo, G.R., and Campos, M.M. (2023). Severe influenza infection is associated with inflammatory programmed cell death in infected macrophages. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1067285"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Corry, J., Kettenburg, G., Upadhyay, A.A., Wallace, M., Marti, M.M., Wonderlich, E.R., Bissel, S.J., Goss, K., Sturgeon, T.J., and Watkins, S.C. (2022). Infiltration of inflammatory macrophages and neutrophils and widespread pyroptosis in lung drive influenza lethality in nonhuman primates. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010395"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Tate, M.D., Ong, J.D.H., Dowling, J.K., McAuley, J.L., Robertson, A.B., Latz, E., Drummond, G.R., Cooper, M.A., Hertzog, P.J., and Mansell, A. (2016). Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition. Sci. Rep., 6.","DOI":"10.1038\/srep27912"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1111\/resp.14141","article-title":"IL-17A is a common and critical driver of impaired lung function and immunopathology induced by influenza virus, rhinovirus and respiratory syncytial virus","volume":"26","author":"Liu","year":"2021","journal-title":"Respirology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/ni.2045","article-title":"Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity","volume":"12","author":"Chang","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.4049\/jimmunol.165.6.3484","article-title":"Respiratory infection with influenza A virus interferes with the induction of tolerance to aeroallergens","volume":"165","author":"Tsitoura","year":"2000","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1111\/cea.12365","article-title":"Influenza A infection enhances antigen-induced airway inflammation and hyperresponsiveness in young but not aged mice","volume":"44","author":"Birmingham","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41467-017-00057-x","article-title":"Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy","volume":"8","author":"To","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.tcb.2013.12.002","article-title":"Trafficking of endosomal Toll-like receptors","volume":"24","author":"Lee","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Stegemann-Koniszewski, S., Behrens, S., Boehme, J.D., Hochnadel, I., Riese, P., Guzm\u00e1n, C.A., Kr\u00f6ger, A., Schreiber, J., Gunzer, M., and Bruder, D. (2018). Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00245"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4711","DOI":"10.4049\/jimmunol.179.7.4711","article-title":"Differential role of TLR- and RLR-signaling in the immune responses to influenza A virus infection and vaccination","volume":"179","author":"Koyama","year":"2007","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.4049\/jimmunol.178.4.2182","article-title":"TLR signaling fine-tunes anti-influenza B cell responses without regulating effector T cell responses","volume":"178","author":"Heer","year":"2007","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10988","DOI":"10.1128\/JVI.01064-12","article-title":"TLR7 recognition is dispensable for influenza virus A infection but important for the induction of hemagglutinin-specific antibodies in response to the 2009 pandemic split vaccine in mice","volume":"86","author":"Kim","year":"2012","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kandasamy, M., Suryawanshi, A., Tundup, S., Perez, J.T., Schmolke, M., Manicassamy, S., and Manicassamy, B. (2016). RIG-I Signaling Is Critical for Efficient Polyfunctional T Cell Responses during Influenza Virus Infection. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005754"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"To, E.E., Erlich, J., Liong, F., Luong, R., Liong, S., Bozinovski, S., Seow, H.J., O\u2019Leary, J.J., Brooks, D.A., and Vlahos, R. (2019). Intranasal and epicutaneous administration of Toll-like receptor 7 (TLR7) agonists provides protection against influenza A virus-induced morbidity in mice. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-38864-5"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e85647","DOI":"10.7554\/eLife.85647","article-title":"TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung antiviral immunity","volume":"12","author":"Jackson","year":"2023","journal-title":"eLife"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eadd4906","DOI":"10.1126\/sciimmunol.add4906","article-title":"Sensing of SARS-CoV-2 by pDCs and their subsequent production of IFN-I contribute to macrophage-induced cytokine storm during COVID-19","volume":"7","author":"Laurent","year":"2022","journal-title":"Sci. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Miles, M.A., Liong, S., Liong, F., Coward-Smith, M., Trollope, G.S., Oseghale, O., Erlich, J.R., Brooks, R.D., Logan, J.M., and Hickey, S. (2023). TLR7 promotes chronic airway disease in RSV-infected mice. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1240552"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/ALN.0000000000002706","article-title":"Toll-like Receptor 7 Contributes to Inflammation, Organ Injury, and Mortality in Murine Sepsis","volume":"131","author":"Jian","year":"2019","journal-title":"Anesthesiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.smim.2011.01.016","article-title":"Toll-like receptor driven B cell activation in the induction of systemic autoimmunity","volume":"23","author":"Green","year":"2011","journal-title":"Semin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1172\/JCI36551","article-title":"Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance","volume":"120","author":"Platonova","year":"2010","journal-title":"J. Clin. Invest."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7349","DOI":"10.1038\/s41467-023-42913-z","article-title":"TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase","volume":"14","author":"Liu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e20201631","DOI":"10.1084\/jem.20201631","article-title":"A TLR7 antagonist restricts interferon-dependent and -independent immunopathology in a mouse model of severe influenza","volume":"218","author":"Rappe","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e68864","DOI":"10.7554\/eLife.68864","article-title":"Dynamically linking influenza virus infection kinetics, lung injury, inflammation, and disease severity","volume":"10","author":"Myers","year":"2021","journal-title":"eLife"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.4049\/jimmunol.1800671","article-title":"Influenza A Virus Infection Causes Chronic Lung Disease Linked to Sites of Active Viral RNA Remnants","volume":"201","author":"Keeler","year":"2018","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.4049\/jimmunol.0802837","article-title":"Acute, but not resolved, influenza A infection enhances susceptibility to house dust mite-induced allergic disease","volume":"182","author":"Fattouh","year":"2009","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tate, M.D., Ioannidis, L.J., Croker, B., Brown, L.E., Brooks, A.G., and Reading, P.C. (2011). The role of neutrophils during mild and severe influenza virus infections of mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017618"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1038\/s41467-019-11249-y","article-title":"Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection","volume":"10","author":"Tang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ajpath.2011.03.013","article-title":"Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis","volume":"179","author":"Narasaraju","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"110456","DOI":"10.1016\/j.celrep.2022.110456","article-title":"Interferon-\u03b3 promotes monocyte-mediated lung injury during influenza infection","volume":"38","author":"Schmit","year":"2022","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.4049\/jimmunol.1701543","article-title":"Inflammatory Monocytes Drive Influenza A Virus-Mediated Lung Injury in Juvenile Mice","volume":"200","author":"Coates","year":"2018","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.it.2017.07.003","article-title":"Neutrophilic Inflammation in Asthma and Association with Disease Severity","volume":"38","author":"Ray","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Britt, R.D., Ruwanpathirana, A., Ford, M.L., and Lewis, B.W. (2023). Macrophages Orchestrate Airway Inflammation, Remodeling, and Resolution in Asthma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310451"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/cea.13811","article-title":"Neutrophilic asthma features increased airway classical monocytes","volume":"51","author":"Niessen","year":"2021","journal-title":"Clin. Exp. Allergy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1165\/rcmb.2014-0255OC","article-title":"Recruited alveolar macrophages, in response to airway epithelial-derived monocyte chemoattractant protein 1\/CCl2, regulate airway inflammation and remodeling in allergic asthma","volume":"52","author":"Lee","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00441-017-2753-2","article-title":"Partners in crime: Neutrophils and monocytes\/macrophages in inflammation and disease","volume":"371","author":"Nicholls","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.cell.2013.03.010","article-title":"Nr4a1-dependent Ly6C(low) monocytes monitor endothelial cells and orchestrate their disposal","volume":"153","author":"Carlin","year":"2013","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Murakami, Y., Fukui, R., Tanaka, R., Motoi, Y., Kanno, A., Sato, R., Yamaguchi, K., Amano, H., Furukawa, Y., and Suzuki, H. (2021). Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.777197"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E5172","DOI":"10.1073\/pnas.1606253113","article-title":"Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus","volume":"113","author":"Finsterbusch","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"24964","DOI":"10.1073\/pnas.2006905117","article-title":"Influenza A virus causes maternal and fetal pathology via innate and adaptive vascular inflammation in mice","volume":"117","author":"Liong","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1093\/intimm\/dxaa055","article-title":"The impact of cell maturation and tissue microenvironments on the expression of endosomal Toll-like receptors in monocytes and macrophages","volume":"32","author":"Sato","year":"2020","journal-title":"Int. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1136\/thoraxjnl-2017-210010","article-title":"Neutrophils drive alveolar macrophage IL-1\u03b2 release during respiratory viral infection","volume":"73","author":"Patel","year":"2018","journal-title":"Thorax"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/mi.2011.35","article-title":"Influenza A facilitates sensitization to house dust mite in infant mice leading to an asthma phenotype in adulthood","volume":"4","author":"Fattouh","year":"2011","journal-title":"Mucosal Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kawaguchi, A., Suzuki, T., Ohara, Y., Takahashi, K., Sato, Y., Ainai, A., Nagata, N., Tashiro, M., and Hasegawa, H. (2017). Impacts of allergic airway inflammation on lung pathology in a mouse model of influenza A virus infection. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173008"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Meng, L., He, X., Zhu, W., Yang, X., Jiang, C., Sun, Q., Raza, M.B.A., Zhang, S., Xue, Q., and Xie, X. (2011). TLR3 and TLR7 modulate IgE production in antigen induced pulmonary inflammation via influencing IL-4 expression in immune organs. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017252"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.jaci.2013.02.041","article-title":"Toll-like receptor 7 gene deficiency and early-life Pneumovirus infection interact to predispose toward the development of asthma-like pathology in mice","volume":"131","author":"Kaiko","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1164\/rccm.201303-0442OC","article-title":"Toll-like receptor 7 rapidly relaxes human airways","volume":"188","author":"Drake","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"L987","DOI":"10.1152\/ajplung.00440.2005","article-title":"TLR7 ligand prevents allergen-induced airway hyperresponsiveness and eosinophilia in allergic asthma by a MYD88-dependent and MK2-independent pathway","volume":"290","author":"Moisan","year":"2006","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jeisy-Scott, V., Davis, W.G., Patel, J.R., Bowzard, J.B., Shieh, W.J., Zaki, S.R., Katz, J.M., and Sambhara, S. (2011). Increased MDSC accumulation and Th2 biased response to influenza A virus infection in the absence of TLR7 in mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025242"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.4049\/jimmunol.1400580","article-title":"Resident alveolar macrophages suppress, whereas recruited monocytes promote, allergic lung inflammation in murine models of asthma","volume":"193","author":"Przybranowski","year":"2014","journal-title":"J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tashiro, H., Takahashi, K., Hayashi, S., Kato, G., Kurata, K., Kimura, S., and Sueoka-Aragane, N. (2016). Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157571"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.4049\/jimmunol.1800881","article-title":"TLR-7 Stress Signaling in Differentiating and Mature Eosinophils Is Mediated by the Prolyl Isomerase Pin1","volume":"201","author":"Shen","year":"2018","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1136\/thoraxjnl-2014-205465","article-title":"Toll-like receptor 7 governs interferon and inflammatory responses to rhinovirus and is suppressed by IL-5-induced lung eosinophilia","volume":"70","author":"Hatchwell","year":"2015","journal-title":"Thorax"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.4049\/jimmunol.165.3.1548","article-title":"CXCR3 expression and activation of eosinophils: Role of IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma","volume":"165","author":"Jinquan","year":"2000","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1164\/rccm.201203-0508OC","article-title":"CXCL10-CXCR3 enhances the development of neutrophil-mediated fulminant lung injury of viral and nonviral origin","volume":"187","author":"Ichikawa","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/cr.2013.25","article-title":"Monoclonal antibody against CXCL-10\/IP-10 ameliorates influenza A (H1N1) virus induced acute lung injury","volume":"23","author":"Wang","year":"2013","journal-title":"Cell Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5278","DOI":"10.4049\/jimmunol.168.10.5278","article-title":"IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma","volume":"168","author":"Medoff","year":"2002","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1165\/rcmb.2006-0231OC","article-title":"IL-2 and IL-18 attenuation of airway hyperresponsiveness requires STAT4, IFN-gamma, and natural killer cells","volume":"36","author":"Matsubara","year":"2007","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Choi, G.E., Lee, B.J., Kwon, S.W., Lee, S.H., Kim, H.S., and Jang, Y.J. (2016). Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis. Sci. Rep., 6.","DOI":"10.1038\/srep27615"},{"key":"ref_66","first-page":"3858032","article-title":"IL-33\/IL-31 Axis: A Potential Inflammatory Pathway","volume":"2018","author":"Casciaro","year":"2018","journal-title":"Mediators Inflamm."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Murdaca, G., Gerosa, A., Paladin, F., Petrocchi, L., Banchero, S., and Gangemi, S. (2021). Vitamin D and Microbiota: Is There a Link with Allergies?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084288"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"432","DOI":"10.4049\/jimmunol.1800396","article-title":"Developmental Regulation of Effector and Resident Memory T Cell Generation during Pediatric Viral Respiratory Tract Infection","volume":"201","author":"Connors","year":"2018","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1189\/jlb.0908559","article-title":"Signaling through TLR7 enhances the immunosuppressive activity of murine CD4+CD25+ T regulatory cells","volume":"87","author":"Forward","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1002\/eji.201040914","article-title":"Treatment with the TLR7 agonist R848 induces regulatory T-cell-mediated suppression of established asthma symptoms","volume":"41","author":"Van","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Thomas, R., Qiao, S., and Yang, X. (2023). Th17\/Treg Imbalance: Implications in Lung Inflammatory Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054865"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ajpath.2011.03.003","article-title":"IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease","volume":"179","author":"Mukherjee","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.4049\/jimmunol.1000733","article-title":"Respiratory virus-induced TLR7 activation controls IL-17-associated increased mucus via IL-23 regulation","volume":"185","author":"Lukacs","year":"2010","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.yhbeh.2010.12.002","article-title":"Sex differences in the response to influenza virus infection: Modulation by stress","volume":"59","author":"Avitsur","year":"2011","journal-title":"Horm. Behav."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13699\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:57:41Z","timestamp":1760115461000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,21]]},"references-count":74,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252413699"],"URL":"https:\/\/doi.org\/10.3390\/ijms252413699","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,21]]}}}