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Harvesting Murine Alveolar Macrophages and Evaluating Cellular Activation Induced by Polyanhydride Nanoparticles
Published on: June 8, 2012
Transcriptome of porcine alveolar macrophages activated by interferon-gamma and lipopolysaccharide
Qiang Liu1, Yong-Li Zhang1, Wei Hu1
1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
Abstract:
The molecular repertoire of porcine alveolar macrophages (PAMs) is greatly affected by the microenvironment they are exposed to, and specifically by inflammatory cytokines, such as interferon gamma (IFN-γ) released by activated lymphocytes, and microbial products, such as lipopolysaccharide (LPS). In our previous study, we found that IFN-γ- and LPS-activated PAMs (M1) could inhibit porcine reproductive and respiratory syndrome virus (PRRSV) replication. In this study, comprehensive analysis of the expression profiles of the genes associated with the polarization of M0-type PAMs (resting) toward M1 phenotypes (activated by IFN-γ and LPS) led to the following main results: 1) 1551 and 1823 genes were upregulated or downregulated in M1-type PAMs, respectively, compared with M0-type PAMs; 2) Among these, genes encoding ASS1 and CRTAM were the most upregulated and downregulated, respectively; 3) Genes involved in cytokine-cytokine receptor interaction and the JAK/STAT signaling pathway were significantly upregulated, suggesting their critical role in cellular activation; and 4) Genes involved in antigen proteolysis and presentation (immunoproteasome subunits), and inhibition of virus replication (host restriction factors) were significantly upregulated, emphasizing the critical role of these cytokines in immunity. Thus, our results provide important information for future studies on the role of PAM polarization in modulation of infection.
Insights
Porcine alveolar macrophages (PAMs) activated by interferon gamma (IFN-γ) and lipopolysaccharide (LPS) show significant gene expression changes, enhancing immune responses against viruses like porcine reproductive and respiratory syndrome virus (PRRSV).
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Porcine alveolar macrophages (PAMs) are crucial immune cells influenced by their microenvironment, including inflammatory cytokines like interferon gamma (IFN-γ) and microbial products like lipopolysaccharide (LPS).
- Previous research demonstrated that M1-polarized PAMs (activated by IFN-γ and LPS) can inhibit porcine reproductive and respiratory syndrome virus (PRRSV) replication.
Purpose of the Study:
- To comprehensively analyze gene expression profiles during the polarization of resting M0-type PAMs to M1 phenotypes.
- To identify key genes and pathways involved in M1 polarization and their role in immune modulation.
Main Methods:
- Gene expression profiling of M0-type PAMs versus M1-type PAMs (activated by IFN-γ and LPS).
- Bioinformatic analysis to identify differentially expressed genes and enriched pathways.
Main Results:
- 1551 genes were upregulated and 1823 genes were downregulated in M1-type PAMs compared to M0-type PAMs.
- Key genes like ASS1 (upregulated) and CRTAM (downregulated) were identified.
- Significant upregulation of genes involved in cytokine-cytokine receptor interaction, JAK/STAT signaling, antigen presentation (immunoproteasome subunits), and host restriction factors.
Conclusions:
- PAM polarization to an M1 phenotype involves substantial molecular changes that enhance cellular activation and immune defense mechanisms.
- Upregulated genes related to immune signaling and viral restriction highlight the critical role of M1 PAMs in combating viral infections like PRRSV.
- These findings provide valuable insights into PAM polarization's role in modulating host-pathogen interactions and infection outcomes.
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