دورية أكاديمية
أعرض في EDS

Dynamically linking influenza virus infection kinetics, lung injury, inflammation, and disease severity.

التفاصيل البيبلوغرافية
العنوان: Dynamically linking influenza virus infection kinetics, lung injury, inflammation, and disease severity.
المؤلفون: Myers MA; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, United States., Smith AP; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, United States., Lane LC; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, United States., Moquin DJ; Department of Anesthesiology, Washington University School of Medicine, St. Louis, United States., Aogo R; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, United States., Woolard S; Flow Cytometry Core, St. Jude Children's Research Hospital, Memphis, United States., Thomas P; Department of Immunology, St. Jude Children's Research Hospital, Memphis, United States., Vogel P; Department of Pathology, St. Jude Children's Research Hospital, Memphis, United States., Smith AM; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, United States.
المصدر: ELife [Elife] 2021 Jul 20; Vol. 10. Date of Electronic Publication: 2021 Jul 20.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: CD8-Positive T-Lymphocytes/*immunology , Inflammation/*pathology , Influenza A Virus, H1N1 Subtype/*immunology , Lung/*pathology , Orthomyxoviridae Infections/*virology, Animals ; Female ; Kinetics ; Linear Models ; Mice ; Mice, Inbred BALB C ; Severity of Illness Index ; Viral Load
مستخلص: Influenza viruses cause a significant amount of morbidity and mortality. Understanding host immune control efficacy and how different factors influence lung injury and disease severity are critical. We established and validated dynamical connections between viral loads, infected cells, CD8 + T cells, lung injury, inflammation, and disease severity using an integrative mathematical model-experiment exchange. Our results showed that the dynamics of inflammation and virus-inflicted lung injury are distinct and nonlinearly related to disease severity, and that these two pathologic measurements can be independently predicted using the model-derived infected cell dynamics. Our findings further indicated that the relative CD8 + T cell dynamics paralleled the percent of the lung that had resolved with the rate of CD8 + T cell-mediated clearance rapidly accelerating by over 48,000 times in 2 days. This complimented our analyses showing a negative correlation between the efficacy of innate and adaptive immune-mediated infected cell clearance, and that infection duration was driven by CD8 + T cell magnitude rather than efficacy and could be significantly prolonged if the ratio of CD8 + T cells to infected cells was sufficiently low. These links between important pathogen kinetics and host pathology enhance our ability to forecast disease progression, potential complications, and therapeutic efficacy.
Competing Interests: MM, AS, LL, DM, RA, SW, PT, PV, AS No competing interests declared
(© 2021, Myers et al.)
التعليقات: Comment in: Elife. 2021 Sep 01;10:. (PMID: 34468313)
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معلومات مُعتمدة: R56 AI125324 United States AI NIAID NIH HHS; K25 AI100946 United States AI NIAID NIH HHS; R01 AI139088 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: CD8 T cells; computational biology; disease severity; immunology; inflammation; influenza virus; lung inflammation; lung injury; mathematical model; systems biology; virus
تواريخ الأحداث: Date Created: 20210720 Date Completed: 20211019 Latest Revision: 20211019
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8370774
DOI: 10.7554/eLife.68864
PMID: 34282728
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.68864