دورية أكاديمية
IL-10 Counteracts IFN-γ to Alleviate Acute Lung Injury in a Viral-Bacterial Superinfection Model.
| العنوان: | IL-10 Counteracts IFN-γ to Alleviate Acute Lung Injury in a Viral-Bacterial Superinfection Model. |
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| المؤلفون: | McKelvey M; Department of Pathology and., Uddin MB; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas., Palani S; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas., Shao S; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas., Sun K; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas. |
| المصدر: | American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2024 Jul; Vol. 71 (1), pp. 110-120. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Thoracic Society Country of Publication: United States NLM ID: 8917225 Publication Model: Print Cited Medium: Internet ISSN: 1535-4989 (Electronic) Linking ISSN: 10441549 NLM ISO Abbreviation: Am J Respir Cell Mol Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2000- : New York, NY : American Thoracic Society Original Publication: [New York, NY : The Association, [c1989- |
| مواضيع طبية MeSH: | Interleukin-10*/metabolism , Interleukin-10*/immunology , Acute Lung Injury*/virology , Acute Lung Injury*/immunology , Acute Lung Injury*/pathology , Acute Lung Injury*/microbiology , Interferon-gamma*/metabolism , Superinfection*/immunology , Superinfection*/virology , Disease Models, Animal*, Animals ; Mice ; Mice, Inbred C57BL ; Methicillin-Resistant Staphylococcus aureus/pathogenicity ; Coinfection/immunology ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/complications ; Orthomyxoviridae Infections/virology ; Staphylococcal Infections/immunology ; Mice, Knockout ; Influenza A virus/immunology ; Lung/virology ; Lung/pathology ; Lung/immunology ; Lung/metabolism |
| مستخلص: | Immune activation is essential for lung control of viral and bacterial infection, but an overwhelming inflammatory response often leads to the onset of acute respiratory distress syndrome. IL-10 plays a crucial role in regulating the balance between antimicrobial immunity and immunopathology. In the present study, we investigated the role of IL-10 in acute lung injury induced by influenza A virus and methicillin-resistant Staphylococcus aureus coinfection. This unique coinfection model resembles patients with acute pneumonia undergoing appropriate antibiotic therapies. Using global IL-10 and IL-10 receptor gene-deficient mice, as well as in vivo neutralizing antibodies, we show that IL-10 deficiency promotes IFN-γ-dominant cytokine responses and triggers acute animal death. Interestingly, this extreme susceptibility is fully preventable by IFN-γ neutralization during coinfection. Further studies using mice with Il10ra deletion in selective myeloid subsets reveal that IL-10 primarily acts on mononuclear phagocytes to prevent IFN-γ/TNF-α hyperproduction and acute mortality. Importantly, this antiinflammatory IL-10 signaling is independent of its inhibitory effect on antiviral and antibacterial defense. Collectively, our results demonstrate a key mechanism of IL-10 in preventing hypercytokinemia and acute respiratory distress syndrome pathogenesis by counteracting the IFN-γ response. |
| التعليقات: | Comment in: Am J Respir Cell Mol Biol. 2024 Jul;71(1):18-20. doi: 10.1165/rcmb.2024-0154ED. (PMID: 38701437) |
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| معلومات مُعتمدة: | R01 HL118408 United States HL NHLBI NIH HHS; R01 HL118408 United States NH NIH HHS |
| فهرسة مساهمة: | Keywords: IL-10; S. aureus; acute lung injury; influenza; pneumonia |
| المشرفين على المادة: | 130068-27-8 (Interleukin-10) 82115-62-6 (Interferon-gamma) 0 (IL10 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240404 Date Completed: 20240701 Latest Revision: 20240707 |
| رمز التحديث: | 20240707 |
| مُعرف محوري في PubMed: | PMC11225870 |
| DOI: | 10.1165/rcmb.2023-0437OC |
| PMID: | 38574279 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1535-4989 |
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| DOI: | 10.1165/rcmb.2023-0437OC |