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| Status |
Public on Dec 31, 2023 |
| Title |
Influenza A virus infection sustainably rewires pneumocyte gene regulatory network responses to different pneumococcal serotypes in secondary Streptococcus pneumoniae infection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Background: Pneumococcal secondary infection following influenza A virus (IAV) pneumonia is a synergistic complication with high mortality. While varying invasiveness of pneumococcal serotypes is an important pathogenic factor, serotype-specifc immediate-early transcriptional responses of the IAV-perturbed alveolar epithelium have not been adressed. We comprehensively analyzed gene transcription in alveolar type II epithelial cells (AECII) isolated from mice infected with IAV and/or S. pneumoniae (S.pn.) serotypes 4, 7F and 19F. Results: IAV, 14 days post infection, rendered the lung susceptible to invasive secondary S.pn. infection with serotypes 4 and 7F but not 19F. Only secondary 7F infection induced exacerbated cytokine/chemokine responses. IAV/7F infection induced superior protein expression of type I and II interferons, acesserbated expression in IAV/serotype 4 infection. Inference of a scale-free-like ARACNE gene co-expression network revealed interferon-response network modules in AECII and network-mapping unfolded S.pn. serotype-specific transcriptional network responses/usage. Secondary S.pn. infection abrogated the IAV-induced pneumocyte proliferative configuration and preceeding IAV infection rendered the transcriptional response to 7F infection comparable to that towards serotype 4. This related especially to network genes correlating with the expression of two master regulators of interferon responses: Irf7 and Stat1. Epigenetic ATAC-seq analysis of AECII in resolved IAV infection identified enhanced expression of ARACNE network genes Hist1h2bf, Igtp, Mki67, Rasl10b, H2-Q6 and H2-Q7 to be associated with increased chromatin accessability at promoter regions. Conclusions: We show that AECII sustainably retain an IAV-associated transcriptional configuration with epigenetic involvement, that serotype-specifically affects proliferation and accelerates and enhances the AECII transcriptional response, mainly to interferons, in secondary S.pn. infection.
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| Overall design |
In total 42 microarrays were analyzed belonging to 14 experimental conditions with 3 independent replicates per condition.
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| Web link |
https://doi.org/10.1101/2023.06.28.546771
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| Contributor(s) |
Boehme JD, Jeron A, Schultz K, Melcher L, Schott K, Gelmez E, Kröger A, Stegemann-Koniszewski S, Bruder D |
| Citation missing |
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| Submission date |
Feb 15, 2023 |
| Last update date |
Apr 03, 2024 |
| Contact name |
Andreas Jeron |
| E-mail(s) |
andreas.jeron@helmholtz-hzi.de
|
| Organization name |
Helmholtz Center for Infection Research
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| Department |
Viral Immunology
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| Lab |
Immune Regulation
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| Street address |
Inhoffenstraße 7
|
| City |
Braunschweig |
| State/province |
Nierdersachsen |
| ZIP/Postal code |
38124 |
| Country |
Germany |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (42)
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| Relations |
| BioProject |
PRJNA935310 |
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