Pseudomonas aeruginosa infection stimulates mitogen-activated protein kinases signaling pathway in human
Gopi Krishnan Gopala Krishnan1, Aiswarya Sethumadhavan1, Pavithra Vellaichamy1
1Cell Signaling Laboratory, Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry, India.
Abstract:
Pseudomonas aeruginosa is a major cause of nosocomial infections and contributes to higher mortality in hospitalized individuals. Infection by P. aeruginosa triggers host immune response through activation of pathogen recognition receptors, which are present in innate cells. Several studies have reported the mechanism of P. aeruginosa induced innate immunity in multiple cell types. But so far there is no reports on response of megakaryocytes to P. aeruginosa infection. Hence, our aim was to investigate the precise role and signaling mechanism of megakaryocytes during P. aeruginosa infection. In this study, we used Mo7e cells as representatives of human megakaryocyte and found that P. aeruginosa infection induces cytotoxicity in these cells. We further demonstrated that P. aeruginosa infection modulates p38 and extracellular signal regulated kinase pathways in Mo7e cells. Protein expression profiling in P. aeruginosa lipopolysaccharide-treated Mo7e cells revealed upregulation of importin subunit β and downregulation of metabolic enzymes. Our results suggest that P. aeruginosa infection regulates mitogen-activated protein kinases signaling pathway and importin in Mo7e cells and that this is a potential mechanism for nuclear translocation of nuclear factor binding near the κ light-chain gene in B cells and c-Jun N-terminal kinases to induce cell cytotoxicity.
Insights
Pseudomonas aeruginosa infection harms human megakaryocytes, impacting cell survival and activating immune signaling pathways. This study reveals novel mechanisms of megakaryocyte response to this common pathogen.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Pseudomonas aeruginosa is a significant cause of hospital-acquired infections.
- Host immune responses to P. aeruginosa involve pathogen recognition receptors in innate cells.
- The response of megakaryocytes to P. aeruginosa infection remains largely uncharacterized.
Purpose of the Study:
- To investigate the role and signaling mechanisms of megakaryocytes during P. aeruginosa infection.
- To elucidate how P. aeruginosa affects megakaryocyte viability and function.
- To identify specific molecular pathways involved in the megakaryocyte response.
Main Methods:
- Utilized Mo7e cells as a model for human megakaryocytes.
- Infected Mo7e cells with Pseudomonas aeruginosa.
- Analyzed cell viability and cytotoxicity.
- Performed protein expression profiling after lipopolysaccharide treatment.
- Investigated modulation of p38 and extracellular signal regulated kinase pathways.
Main Results:
- P. aeruginosa infection induced significant cytotoxicity in Mo7e cells.
- The infection modulated the p38 and extracellular signal regulated kinase (ERK) pathways.
- Protein expression profiling showed upregulation of importin subunit β and downregulation of metabolic enzymes.
- Identified potential mechanisms involving mitogen-activated protein kinases (MAPK) signaling and importin.
Conclusions:
- P. aeruginosa infection impacts megakaryocyte viability through cytotoxicity.
- The mitogen-activated protein kinases (MAPK) signaling pathway and importin are key players in the megakaryocyte response.
- These pathways may facilitate nuclear translocation leading to cytotoxicity.
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