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Effects of Klebsiella pneumoniae Bacteriophages on IRAK3 Knockdown/Knockout THP-1 Monocyte Cell Lines
Bryce Dylan Schubert1, Heng Ku2, Mwila Kabwe1,3
1Department of Rural Clinical Sciences, La Trobe Rural Health School, La Trobe University, P.O. Box 199, Bendigo, VIC 3550, Australia.
Abstract:
Bacterial sepsis characterised by an immunosuppressive and cytokine storm state is a challenge to treat clinically. While conventional antibiotics have been associated with exacerbating the cytokine storm, the role that bacteriophages may play in immune modulation of sepsis remains unclear. Bacteriophages are bacterial viruses that have the capacity to lyse specific bacteria and hence provide a natural alternative to antibiotics. K. pneumoniae is known to cause sepsis in humans, and in this study we isolated two lytic bacteriophages against this pathogen, one of which was a novel jumbo bacteriophage. We employed THP-1 monocyte cell lines, with different functional phenotypes for the interleukin-1 receptor associated kinase 3 (IRAK3- a cytoplasmic homeostatic mediator and prognostic marker of inflammation), to evaluate the role of the K. pneumoniae bacteriophages in modulating the immune response in-vitro. We showed for the first time that bacteriophages did not stimulate excessive production of tumour necrosis factor alpha, or interleukin-6, in THP-1 monocyte cell lines which displayed varying levels of IRAK3 expression.
Insights
Bacteriophages offer a potential alternative to antibiotics for treating sepsis. This study found that bacteriophages targeting Klebsiella pneumoniae did not worsen the inflammatory cytokine storm in immune cells.
Area of Science:
- Microbiology
- Immunology
- Virology
Background:
- Bacterial sepsis presents a clinical challenge due to immunosuppression and cytokine storms.
- Conventional antibiotics may exacerbate sepsis-induced cytokine storms.
- The immunomodulatory role of bacteriophages in sepsis is not well understood.
Purpose of the Study:
- To investigate the immunomodulatory effects of bacteriophages against Klebsiella pneumoniae in vitro.
- To determine if bacteriophages exacerbate or mitigate inflammatory responses in immune cells.
Main Methods:
- Isolation of two lytic bacteriophages against Klebsiella pneumoniae, including a novel jumbo bacteriophage.
- Utilizing THP-1 monocyte cell lines with varying expression of interleukin-1 receptor associated kinase 3 (IRAK3).
- Assessing the production of tumor necrosis factor alpha and interleukin-6 in response to bacteriophage treatment.
Main Results:
- Bacteriophages did not induce excessive production of tumor necrosis factor alpha or interleukin-6.
- This effect was observed across THP-1 cell lines with different IRAK3 expression levels.
- Demonstrates a lack of pro-inflammatory cytokine storm exacerbation by these bacteriophages.
Conclusions:
- Bacteriophages targeting K. pneumoniae do not appear to exacerbate the cytokine storm in this in vitro model.
- These findings suggest bacteriophages may be a safer alternative for sepsis treatment compared to antibiotics.
- Further research into bacteriophage-host immune interactions is warranted for sepsis therapy.
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