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Adjuvant Activity of Mycobacterium paratuberculosis in Enhancing the Immunogenicity of Autoantigens During Experimental Autoimmune Encephalomyelitis
Published on: May 12, 2023
Purified PTP1 protein induces antigen-specific protective immunity against Encephalitozoon cuniculi
Magali M Moretto1, Elizabeth M Lawlor, Yanji Xu
1Department of Microbiology, Immunology and Tropical Medicine, George Washington University, WA 20037, USA.
Abstract:
Microsporidiosis poses a problem for immunocompromised individuals including patients with HIV infection as well as those with organ transplantation. Recent reports from Africa have suggested that microsporidiosis with diarrhea is an independent risk factor for malnutrition in children. Previous studies from our laboratory have demonstrated that CD8(+) T cells are an essential component of protective immunity against the microsporidium Encephalitozoon cuniculi. Mutant mice lacking this T cell subset or cytotoxic function are unable to clear the infection and ultimately succumb to the disease. However, information regarding the antigens involved in the elicitation of CD8(+) T cell response is not available. In this study, we report that immunization of animals with Encephalitozoon hellem polar tube protein 1 (rEhPTP1) induces a strong T cell response in vaccinated animals. Splenic dendritic cells pulsed with rEhPTP1 are able to induce E. cuniculi specific CD8(+) T cell response with no effect on the CD4(+) T cell subset. This is the first report identifying a protein capable of inducing CD8(+) T cell immunity, which is conserved in other microsporidial species of human importance.
Insights
Researchers identified a key protein, Encephalitozoon hellem polar tube protein 1 (rEhPTP1), that triggers a crucial CD8(+) T cell immune response against microsporidiosis. This finding is vital for developing new treatments for immunocompromised individuals.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Microsporidiosis is a significant opportunistic infection in immunocompromised individuals, including those with HIV/AIDS and organ transplant recipients.
- Diarrhea caused by microsporidiosis is linked to malnutrition in children, highlighting its public health impact.
- Previous research established CD8(+) T cells as critical for immunity against Encephalitozoon cuniculi, but the specific antigens involved were unknown.
Purpose of the Study:
- To identify antigens capable of eliciting a protective CD8(+) T cell response against microsporidiosis.
- To investigate the role of Encephalitozoon hellem polar tube protein 1 (rEhPTP1) in inducing cell-mediated immunity.
Main Methods:
- Immunization of animals with purified recombinant Encephalitozoon hellem polar tube protein 1 (rEhPTP1).
- Assessment of T cell responses, specifically focusing on CD8(+) and CD4(+) T cell subsets.
- Utilizing splenic dendritic cells pulsed with rEhPTP1 to evaluate their capacity to induce antigen-specific T cell responses.
Main Results:
- Immunization with rEhPTP1 successfully induced a robust T cell response in vaccinated animals.
- rEhPTP1-pulsed dendritic cells effectively stimulated Encephalitozoon cuniculi-specific CD8(+) T cells.
- No significant impact on the CD4(+) T cell subset was observed, indicating a specific CD8(+) T cell-mediated response.
Conclusions:
- Encephalitozoon hellem polar tube protein 1 (rEhPTP1) is identified as a potent antigen for inducing CD8(+) T cell immunity against microsporidiosis.
- This protein represents a promising candidate for developing novel vaccines or immunotherapies targeting microsporidial infections.
- The identified antigen is conserved across important human microsporidial species, suggesting broad applicability.
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