Time-course transcriptome analysis of lungs from mice infected with inhaled aerosolized Stenotrophomonas maltophilia
Guangyang Xu1,2,3,4, Hui Liu2, Dunling Xia1
1The First Clinical College of Anhui Medical University, Hefei, China.
Background:
Stenotrophomonas maltophilia (SMA) has emerged as an important pathogen capable of causing an opportunistic and nosocomial infection. We performed RNA sequencing (RNA-seq) of lung tissues from mice with pulmonary SMA infection over time via aerosolized intratracheal inhalation to investigate transcription profile changes in SMA-infected lungs.
Methods:
A mouse model of acute lethal SMA pneumonia was established in this study using aerosolized intratracheal inhalation, laying the groundwork for future SMA research. RNA-seq was then used to create a transcriptional profile of the lungs of the model mice at 0, 4, 12, 24, 48, and 72 hours post-infection (hpi). Mfuzz time clustering, weighted gene coexpression network analysis (WGCNA), and Immune Cell Abundance Identifier for mouse (ImmuCellAI-mouse) were used to analyze RNA-seq data.
Results:
A gradual change in the lung transcriptional profile was observed, which was consistent with the expected disease progression. At 4 hpi, the expression of genes related to the acute phase inflammatory response increased, as predicted abundance of innate immune cells. At this stage, an increased demand for energy was also observed, including an increase in the expression of genes involved in circulation, muscle function and mitochondrial respiratory chain function. The expression of genes associated with endoplasmic reticulum stress (ERS) and autophagy increased at 24 hpi. Unlike the number of natural killer (NK) cells following most bacterial lung infections, the abundance of NK cells decreased following infection with SMA. The expression levels of Cxcl10, Cd14, Gbp5, Cxcr2, Tnip1, Zc3h12a, Egr1, Sell and Gbp2 were high and previously unreported in SMA pneumonia, and they may be important targets for future studies.
Conclusions:
To our knowledge, this is the first study to investigate the pulmonary transcriptional response to SMA infection. The findings shed light on the molecular mechanisms underlying the pathogenesis of SMA pneumonia, which may aid in the development of therapies to reduce the occurrence of SMA pulmonary infection.
Insights
This study reveals dynamic changes in lung gene expression during Stenotrophomonas maltophilia (SMA) pneumonia in mice. Key inflammatory and metabolic pathways are activated, with a unique decrease in natural killer cells, offering new therapeutic targets.
Area of Science:
- Microbiology
- Immunology
- Genomics
Background:
- Stenotrophomonas maltophilia (SMA) is an opportunistic pathogen causing nosocomial infections.
- Pulmonary infections by SMA are a growing clinical concern.
Purpose of the Study:
- To investigate the dynamic transcriptional changes in mouse lungs following pulmonary SMA infection.
- To establish a mouse model for studying SMA pneumonia.
Main Methods:
- A mouse model of acute lethal SMA pneumonia was established via aerosolized intratracheal inhalation.
- RNA sequencing (RNA-seq) was performed on lung tissues at multiple time points post-infection (0-72 hours).
- Bioinformatic analyses included Mfuzz time clustering, WGCNA, and ImmuCellAI-mouse for immune cell abundance.
Main Results:
- Lung transcriptional profiles showed gradual changes consistent with disease progression.
- Early infection (4 hpi) revealed increased expression of acute phase inflammatory response genes and heightened energy metabolism.
- Later infection (24 hpi) showed increased endoplasmic reticulum stress and autophagy markers, with a notable decrease in natural killer cell abundance.
Conclusions:
- This is the first study to detail the pulmonary transcriptional response to SMA infection.
- Findings elucidate molecular mechanisms of SMA pneumonia pathogenesis.
- Identified key genes (e.g., Cxcl10, Cd14, Gbp5) may serve as future therapeutic targets.
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