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Author Spotlight: Creating a Versatile Experimental Autoimmune Encephalomyelitis Model Relevant for Both Male and Female Mice
Published on: October 13, 2023
Characterization of a Murine Model for Encephalitozoon hellem Infection after Dexamethasone Immunosuppression
Guozhen An1,2, Yunlin Tang1,2, Biying Mo1,2
1State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
Background:
Encephalitozoon hellem (E. hellem) belongs to a group of opportunistic pathogens called microsporidia. Microsporidia infection symptoms vary and include diarrhea, ocular disorders and systemic inflammations. Traditionally, immunodeficient animals were used to study microsporidia infection. To overcome the difficulties in maintenance and operation using immunodeficient mice, and to better mimic natural occurring microsporidia infection, this study aims to develop a pharmacologically immunosuppressed murine model of E. hellem infection.
Methods:
Wild-type C57BL/6 mice were immunosuppressed with dexamethasone (Dex) and then E. hellem spores were inoculated into the mice intraperitoneally. Control groups were the Dex-immunosuppressed but noninoculated mice, and the Dex-immunosuppressed then lipopolysaccharide (LPS)-treated mice. Mice body weights were monitored and all animals were sacrificed at the 15th day after inoculation. Tissue fragments and immune cells were collected and processed.
Results:
Histopathological analysis demonstrated that E. hellem inoculation resulted in a disseminated nonlethal infection. Interestingly, E. hellem infection desensitized the innate immunity of the host, as shown by cytokine expressions and dendritic cell maturation. We also found that E. hellem infection greatly altered the composition of host gut microbiota. (4) Conclusions: Dex-immunosuppressed mice provide a useful tool for study microsporidiosis and the interactions between microsporidia and host immunity.
Insights
This study developed a new mouse model for Encephalitozoon hellem (E. hellem) infection using dexamethasone immunosuppression. The model revealed E. hellem infection alters host immunity and gut microbiota composition.
Area of Science:
- Immunology
- Microbiology
- Pathogen Research
Background:
- Encephalitozoon hellem (E. hellem) is an opportunistic microsporidian pathogen.
- Microsporidiosis presents with diverse symptoms, including diarrhea, ocular issues, and systemic inflammation.
- Traditional animal models for microsporidia research often involve immunodeficient mice, posing maintenance challenges.
Purpose of the Study:
- To develop a pharmacologically immunosuppressed murine model for E. hellem infection.
- To better simulate natural microsporidial infections compared to traditional models.
- To investigate the host-pathogen interactions in a controlled experimental setting.
Main Methods:
- Wild-type C57BL/6 mice were immunosuppressed using dexamethasone (Dex).
- E. hellem spores were administered intraperitoneally to immunosuppressed mice.
- Control groups included non-inoculated immunosuppressed mice and immunosuppressed mice treated with lipopolysaccharide (LPS).
Main Results:
- Histopathology confirmed disseminated, nonlethal E. hellem infection in the developed model.
- E. hellem infection was observed to desensitize host innate immunity, indicated by altered cytokine expression and dendritic cell maturation.
- Significant alterations in host gut microbiota composition were detected following E. hellem infection.
Conclusions:
- Dexamethasone-immunosuppressed mice serve as a valuable model for studying microsporidiosis.
- This model facilitates research into the complex interactions between microsporidia and host immune responses.
- The findings highlight the impact of E. hellem on host immunity and gut microbiome dynamics.
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