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Published on: December 7, 2019
T cell activation status determines the cytokine pattern induced by zymosan and bacterial DNA both in thymocytes and
C Zimmermann1, A Weber, A K Mausberg
1Department of Neurology, Heinrich Heine University, Düsseldorf, Germany.
Abstract:
Proinflammatory cytokines are essential mediators of the immunopathology associated with microbial sepsis. The fungal cell wall component zymosan and bacterial DNA are well-studied experimental tools for investigating these processes, simulating the presence of fungal or bacterial infection. Cells of the immune periphery, but also immune cells in the thymus, are affected essentially by the presence of microbes or their immune stimuli in sepsis. For this reason, we investigated the cytokine pattern present in the spleen (containing mature immune cells) and the thymus (containing immature immune cells) upon exposure to zymosan and Escherichia coli DNA. To study the role of T cell activation status, we investigated ex-vivo cultures with and without αCD3 stimulation for changes in their cytokine secretion pattern as measured by cytokine enzyme-linked immunospot (ELISPOT) and flow cytometry analysis. We found that both substances strongly co-stimulate αCD3-induced interferon (IFN)-γ and interleukin (IL)-6 secretion in the thymus and in the spleen, but stimulate IL-17 production only moderately. Moreover, zymosan increases PLP peptide (PLPp)-specific IFN-γ and IL-6 production in experimental autoimmune encephalomyelitis (EAE) induced in Swiss Jim Lambert (SJL)/J mice, confirming that T cell activation status is crucial for the cytokines secreted by an immune cell population encountering a microbial pathogen or immunostimulating parts of it.
Insights
Microbial stimuli like zymosan and bacterial DNA significantly enhance T cell activation, boosting interferon-gamma (IFN-γ) and interleukin-6 (IL-6) cytokine production in both the spleen and thymus.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Proinflammatory cytokines are key in sepsis immunopathology.
- Zymosan (fungal) and bacterial DNA are used to model microbial infections.
- Immune cells in the periphery and thymus are impacted during sepsis.
Purpose of the Study:
- To investigate cytokine patterns in the spleen and thymus in response to zymosan and E. coli DNA.
- To determine the role of T cell activation status on cytokine secretion.
Main Methods:
- Ex-vivo cultures of spleen and thymus cells were stimulated with zymosan and E. coli DNA, with and without αCD3 stimulation.
- Cytokine secretion was measured using enzyme-linked immunospot (ELISPOT) and flow cytometry.
- Experimental autoimmune encephalomyelitis (EAE) models were used to assess PLP peptide-specific responses.
Main Results:
- Both zymosan and E. coli DNA strongly co-stimulated αCD3-induced interferon (IFN)-γ and interleukin (IL)-6 secretion in thymus and spleen.
- Moderate stimulation of IL-17 production was observed.
- Zymosan enhanced PLP peptide-specific IFN-γ and IL-6 production in EAE models.
Conclusions:
- T cell activation status is critical for the cytokine profile produced by immune cells upon encountering microbial components.
- Sepsis-related microbial stimuli significantly influence cytokine production in both mature and immature immune cell populations.
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