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Updated: Jun 5, 2026
A Non-invasive and Technically Non-intensive Method for Induction and Phenotyping of Experimental Bacterial Pneumonia in Mice
Published on: September 28, 2016
Interferon-γ production by neutrophils during bacterial pneumonia in mice
Mitsuhiro Yamada1, John C Gomez, Pauline E Chugh
1Center for Airways Disease, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7248, USA.
Rationale:
Neutrophils are usually the first circulating leukocytes to respond during bacterial pneumonia. Their expression of oxidants, proteases, and other mediators present in granules is well documented, but their ability to produce mediators through transcription and translation after migration to an inflammatory site has been appreciated only more recently. Interferon (IFN)-γ is a cytokine with many functions important in host defense and immunity.
Objectives:
To examine the expression and function of IFN-γ in bacterial pneumonias.
Methods:
IFN-γ mRNA and protein were measured in digests of mouse lungs with 24-hour bacterial pneumonia. Bacterial clearance was studied with IFN-γ-deficient mice.
Measurements And Main Results:
Streptococcus pneumoniae and Staphylococcus aureus each induce expression of IFN-γ mRNA and protein by neutrophils by 24 hours. Only neutrophils that have migrated into pneumonic tissue produce IFN-γ. Deficiency of Hck/Fgr/Lyn, Rac2, or gp91(phox) prevents IFN-γ production. IFN-γ enhances bacterial clearance and is required for formation of neutrophil extracellular traps. In contrast, Pseudomonas aeruginosa and Escherichia coli induce production of IFN-γ mRNA but not protein. During pneumonia induced by E. coli but not S. pneumoniae, neutrophils produce microRNAs that target the 3' untranslated region of the IFN-γ gene.
Conclusions:
S. pneumoniae and S. aureus, but not P. aeruginosa and E. coli, induce emigrated neutrophils to produce IFN-γ within 24 hours. Hck/Fgr/Lyn, Rac2, and NADPH oxidase are required for IFN-γ production. IFN-γ facilitates bacterial clearance at least in part through regulating formation of neutrophil extracellular traps. Differential expression by neutrophils of microRNAs that target the 3' untranslated region of the IFN-γ gene may contribute to the pathogen-specific regulation of translation.
Insights
Certain bacteria, like Streptococcus pneumoniae, trigger neutrophils to produce Interferon (IFN)-γ, enhancing bacterial clearance. This IFN-γ production is crucial for host defense during pneumonia.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Neutrophils are key immune cells in bacterial pneumonia.
- While granule mediators are known, neutrophil de novo mediator production post-migration is a newer focus.
- Interferon (IFN)-γ is a critical cytokine for host defense and immunity.
Purpose of the Study:
- To investigate the expression and functional role of IFN-γ in bacterial pneumonia models.
Main Methods:
- Quantified IFN-γ mRNA and protein in mouse lungs with bacterial pneumonia.
- Assessed bacterial clearance using IFN-γ-deficient mice.
Main Results:
- Streptococcus pneumoniae and Staphylococcus aureus induced IFN-γ mRNA and protein in emigrated neutrophils within 24 hours.
- IFN-γ production by neutrophils requires Hck/Fgr/Lyn, Rac2, and NADPH oxidase.
- IFN-γ enhanced bacterial clearance and neutrophil extracellular trap formation.
- Pseudomonas aeruginosa and Escherichia coli induced IFN-γ mRNA but not protein; E. coli pneumonia involved neutrophil microRNAs targeting IFN-γ mRNA.
Conclusions:
- Specific bacteria (S. pneumoniae, S. aureus) induce neutrophil IFN-γ production, essential for bacterial clearance, partly via neutrophil extracellular traps.
- Pathogen-specific regulation of IFN-γ translation involves neutrophil microRNAs.
