Altered transcriptional responses in the lungs of aged mice after influenza infection.
JournalImmunity & Ageing : I & A
MetadataShow full item record
AbstractBackground: Influenza causes a serious infection in older individuals who are at the highest risk for mortality from this virus. Changes in the immune system with age are well known. This study used transcriptomic analysis to evaluate how aging specifically affects the functional host response to influenza in the lung. Adult (12-16 weeks) and aged (72-76 weeks) mice were infected with influenza and lungs were processed for RNA analysis. Results: Older mice demonstrated a delayed anti-viral response on the level of transcription compared to adults, similar to the immunologic responses measured in prior work. The transcriptional differences, however, were evident days before observable differences in the protein responses described previously. The transcriptome response to influenza in aged mice was dominated by immunoglobulin genes and B cell markers compared to adult animals, suggesting immune dysregulation. Despite these differences, both groups of mice had highly similar transcriptional responses involving non-immune genes one day after inoculation and T cell genes during resolution. Conclusions: These results define a delayed and dysregulated immune response in the lungs of aged mice infected with influenza. The findings implicate B cells and immunoglobulins as markers or mechanisms of immune aging. In addition to discovering new therapeutic targets, the findings underscore the value of transcription studies and network analysis to characterize complex biological processes, and serve as a model to analyze the susceptibility of the elderly to infectious agents.
Data AvailibilityRNA expression data and sample metadata are deposited in the GEO data repository under accession: GSE197596. A script to recapitulate the analysis is available upon request.
Rights/Terms© 2022. The Author(s).
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/19081
- Discrete Dynamical Modeling of Influenza Virus Infection Suggests Age-Dependent Differences in Immunity.
- Authors: Keef E, Zhang LA, Swigon D, Urbano A, Ermentrout GB, Matuszewski M, Toapanta FR, Ross TM, Parker RS, Clermont G
- Issue date: 2017 Dec 1
- Suppression of Cytotoxic T Cell Functions and Decreased Levels of Tissue-Resident Memory T Cells during H5N1 Infection.
- Authors: Kandasamy M, Furlong K, Perez JT, Manicassamy S, Manicassamy B
- Issue date: 2020 Apr 16
- Impaired immune responses in the lungs of aged mice following influenza infection.
- Authors: Toapanta FR, Ross TM
- Issue date: 2009 Nov 18
- Differential pulmonary transcriptomic profiles in murine lungs infected with low and highly virulent influenza H3N2 viruses reveal dysregulation of TREM1 signaling, cytokines, and chemokines.
- Authors: Ivan FX, Rajapakse JC, Welsch RE, Rozen SG, Narasaraju T, Xiong GM, Engelward BP, Chow VT
- Issue date: 2012 Mar
- Unique Transcriptional Architecture in Airway Epithelial Cells and Macrophages Shapes Distinct Responses following Influenza Virus Infection Ex Vivo.
- Authors: Ma JZ, Ng WC, Zappia L, Gearing LJ, Olshansky M, Pham K, Cheong K, Hsu A, Turner SJ, Wijburg O, Londrigan SL, Brooks AG, Reading PC
- Issue date: 2019 Mar 15