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.
Highlights
Tuberculosis (TB) is a major public health problem and remains one of the major causes of mortality from an infectious disease worldwide
For the phenotypic characterization of the APCs that were pulsed with Hsp65 messenger RNA (mRNA), electroporated cells or APCs that were electroporated with Hsp65 mRNA, we evaluated the expression of cell surface markers
The cells recovered from mice immunized with Hsp65 mRNAtransfected macrophages were able to produce only IL-5 (Figure 3D)
Summary
Tuberculosis (TB) is a major public health problem and remains one of the major causes of mortality from an infectious disease worldwide. About one-third of the world’s population has been infected with Mycobacterium tuberculosis. The greatest difficulty in the treatment of TB is the necessity of continuous medication over a long period of time with multiple drugs [1]. Most patients are averse or unable to complete a full course of medication, and patients who do not consistently undergo their therapies are at risk of relapsing and acquiring multidrug-resistant TB [1,2]. Immunotherapy has been proposed as an alternative to treat TB, especially drug-sensitive TB. Immunotherapy that enhances the efficiency of the immune response in M. tuberculosis-infected patients could be of additional value as a strategy to complement anti-bacterial chemotherapy. Various nonspecific or antigen-specific immunological agents, such as DNA plasmids [3,4], cytokines [5], immunoglobulins [6], and mycobacterial antigens [7], have been used either alone or as adjuncts to chemotherapeutic regimens with varying success rates
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