| Title |
Modular Transcriptional Networks of the Host Pulmonary Response during Early and Late Pneumococcal Pneumonia
|
|---|---|
| Published in |
Molecular Medicine, May 2015
|
| DOI | 10.2119/molmed.2014.00263 |
| Pubmed ID | |
| Authors |
Brendon P. Scicluna, Miriam H. van Lieshout, Dana C. Blok, Sandrine Florquin, Tom van der Poll |
| Abstract |
Streptococcus pneumoniae (Spneu) remains the most lethal bacterial pathogen and the dominant agent of community-acquired pneumonia. Treatment has perennially focused on the use of antibiotics; albeit scrutinized due to the occurrence of antibiotic-resistant Spneu strains. Immunomodulatory strategies have emerged as potential treatment options. Although promising, immunomodulation can lead to improper tissue functions either at steady-state or upon infectious challenge. This argues for the availability of tools to enable a detailed assessment of whole pulmonary functions during the course of infection, not only those functions biased to the defense response. Thus, through the use of an unbiased tissue microarray and bioinformatics approach, we aimed to construct a comprehensive map of whole lung transcriptional activity and cellular pathways during the course of pneumococcal pneumonia. We performed genome-wide transcriptional analysis of whole lungs before, 6- and 48-hours after Spneu infection in mice. The 4000 most variable transcripts across all samples were used to assemble a gene co-expression network comprised of 13 inter-correlating modules (clusters of genes). 54% of this whole lung transcriptional network was altered upon 6- and 48-hours Spneu infection. Canonical signaling pathway analysis uncovered known pathways imparting protection, including IL17A/IL17F signaling, and previously undetected mechanisms that included lipid metabolism. Through in silico prediction of cell-types, pathways were observed to enrich for distinct cell-types such as a novel stromal cell lipid metabolism pathway. These cellular mechanisms were furthermore anchored at functional hub genes of cellular fate, differentiation, growth and transcription. Collectively, we provide a benchmark unsupervised map of whole lung transcriptional relationships and cellular activity during early and late pneumococcal pneumonia. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 19 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 26% |
| Student > Ph. D. Student | 4 | 21% |
| Student > Doctoral Student | 3 | 16% |
| Student > Bachelor | 2 | 11% |
| Other | 2 | 11% |
| Other | 1 | 5% |
| Unknown | 2 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 26% |
| Agricultural and Biological Sciences | 3 | 16% |
| Biochemistry, Genetics and Molecular Biology | 1 | 5% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
| Veterinary Science and Veterinary Medicine | 1 | 5% |
| Other | 4 | 21% |
| Unknown | 4 | 21% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 May 2015.
All research outputs
#17,758,791
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Outputs from Molecular Medicine
#881
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Outputs of similar age
#179,477
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Outputs of similar age from Molecular Medicine
#12
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