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Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat experimental tuberculosis
C D Rocha1, A P F Trombone, J C C Lorenzi
1Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Abstract:
In the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with DNA or RNA. However, comparative studies suggest that transfecting dendritic cells with messenger RNA (mRNA) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. In the present study, we evaluated a new therapeutic strategy to fight tuberculosis using dendritic cells and macrophages transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells transfected with Hsp65 mRNA exhibit a higher level of expression of co-stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory properties. We also demonstrated that spleen cells obtained from animals immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to generate a mixed Th1/Th2 response with production not only of IFN-γ but also of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65 mRNA-transfected macrophages were able to produce only IL-5. When mice were infected with Mycobacterium tuberculosis and treated with antigen-presenting cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect any decrease in the lung bacterial load or any preservation of the lung parenchyma, indicating the inability of transfected cells to confer curative effects against tuberculosis. In spite of the lack of therapeutic efficacy, this study reports for the first time the use of antigen-presenting cells transfected with mRNA in experimental tuberculosis.
Insights
Messenger RNA (mRNA)-transfected antigen-presenting cells show immunostimulatory properties but failed to provide therapeutic benefits against tuberculosis in mice. Further research is needed to explore their potential in treating mycobacterial infections.
Area of Science:
- Immunology
- Vaccinology
- Infectious Diseases
Background:
- Dendritic cells are explored for cancer therapy, with mRNA transfection emerging as a superior antigen-loading method.
- Messenger RNA (mRNA) transfection of antigen-presenting cells (APCs) is a promising strategy for immunotherapy.
Purpose of the Study:
- To evaluate the therapeutic potential of Hsp65 mRNA-transfected dendritic cells and macrophages against tuberculosis.
- To investigate the immunostimulatory properties and immune response generated by Hsp65 mRNA-transfected APCs.
Main Methods:
- Transfection of dendritic cells and macrophages with Hsp65 mRNA.
- Assessment of co-stimulatory molecule expression on transfected APCs.
- Immunization of mice with transfected APCs, followed by infection with Mycobacterium tuberculosis.
- Analysis of immune responses (cytokine production) and lung pathology.
Main Results:
- Hsp65 mRNA transfection increased co-stimulatory molecule expression on APCs, indicating immunostimulatory effects.
- Immunization with Hsp65 mRNA-transfected dendritic cells induced a mixed Th1/Th2 immune response (IFN-γ, IL-5, IL-10).
- Immunization with Hsp65 mRNA-transfected macrophages induced a Th2-biased response (IL-5 only).
- No reduction in lung bacterial load or lung parenchyma preservation was observed in treated mice.
Conclusions:
- Hsp65 mRNA-transfected APCs possess immunostimulatory properties but do not confer curative effects against experimental tuberculosis.
- This study is the first to report the use of mRNA-transfected APCs in experimental tuberculosis.
- Further investigation is required to optimize mRNA-based immunotherapy for tuberculosis.
