Toxoplasma gondii could have a possible role in the cancer mechanism by modulating the host's cell response
1Department of Parasitology, Ege University Medical School, Izmir, Turkey; Cancer Research Center, Ege University, Izmir, Turkey; Department of Basic Oncology, Ege University, Institute of Health Sciences, Izmir, Turkey; Department of Bioinformatics, Ege University, Institute of Health Sciences, Izmir, Turkey; Departments of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, ABD.
Abstract:
Toxoplasma gondii, which manipulates many signaling pathways to achieve persistence in host cells, is intimately linked to immune and inflammation responses. However, there is still lack of information about the impact of T. gondii on cellular and immune responses. This study was designed to seek the impact of T. gondii infection causing life-long inflammation in brain, on cancer mechanism. To identify molecular effects of the T. gondii and understand the association between the functional perturbations occurring during infection and cancer development, the transcriptomic datasets obtained mice infected with T. gondii were downloaded from GEO. The differentially expressed genes (DEGs) were identified and functional enrichment analysis was performed using IPA platform, then all results were evaluated with comparison analyses. Subsequently, a T. gondii infection model with human neuroepithelioma cell culture was performed in order to validate top DEGs participated in common networks/pathways in cancer mechanism. Transcriptomic analyses of infected mice and in vitro cell culture model revealed a strong immune response and inflammation occurred by parasite-induced damage and parasite-associated immunopathology in host cell and tissue. T. gondii infection could modulate certain signaling pathways of host, which were also common to those perturbed in carcinogenesis. Interestingly, the network analysis of the data sets predicted an activation in development of solid cancer vice versa inhibition in hematological cancer during T. gondii infection. Parasite might also control the tumor growth due to its potent immune-stimulant effects. As result, T. gondii infection generating a continual inflammation in tissues might potentially contribute to cancer development by regulating critical host signaling pathways or reveal an anti-tumoral activity.
Insights
Toxoplasma gondii infection causes inflammation and alters host cell signaling pathways. This parasite may promote solid cancer development while inhibiting blood cancers, potentially impacting tumor growth.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Toxoplasma gondii manipulates host cell signaling pathways for persistence.
- The impact of T. gondii on cellular and immune responses, particularly concerning cancer mechanisms, remains unclear.
- Chronic inflammation induced by T. gondii in the brain is a key area of investigation.
Purpose of the Study:
- To investigate the impact of T. gondii infection on cancer mechanisms.
- To identify molecular effects of T. gondii and its association with cancer development.
- To understand the role of T. gondii in modulating host signaling pathways relevant to carcinogenesis.
Main Methods:
- Downloaded and analyzed transcriptomic datasets from T. gondii-infected mice (GEO database).
- Identified differentially expressed genes (DEGs) and performed functional enrichment analysis using IPA.
- Validated top DEGs in a T. gondii infection model using human neuroepithelioma cell culture.
Main Results:
- Transcriptomic analyses revealed a strong immune response and inflammation due to parasite-induced damage and immunopathology.
- T. gondii infection modulates host signaling pathways common to carcinogenesis.
- Network analysis predicted activation of solid cancer development and inhibition of hematological cancer.
Conclusions:
- T. gondii infection induces chronic inflammation and modulates host signaling pathways, potentially contributing to cancer development.
- The parasite may exhibit dual roles in cancer, promoting solid tumors while inhibiting hematological malignancies.
- T. gondii's immune-stimulant effects could influence tumor growth, warranting further investigation into its anti-tumoral potential.
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