Related Experiment Videos
Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA
I Tsunoda1, N D Tolley, D J Theil
1Department of Neurology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Abstract:
Theiler's murine encephalomyelitis virus (TMEV) infection and relapsing-remitting experimental allergic encephalomyelitis (R-EAE) have been used to investigate the viral and autoimmune etiology of multiple sclerosis (MS), a possible Th1-type mediated disease. DNA immunization is a novel vaccination strategy in which few harmful effects have been reported. Bacterial DNA and oligodeoxynucleotides, which contain CpG motifs, have been reported to enhance immunostimulation. Our objectives were two-fold: first, to ascertain whether plasmid DNA, pCMV, which is widely used as a vector in DNA immunization studies, could exert immunostimulation in vitro; and second, to test if pCMV injection could modulate animal models for MS in vivo. We demonstrated that this bacterially derived DNA could induce interleukin (IL)-12, interferon (IFN)gamma, (Th1-promoting cytokines), and IL-6 production as well as activate NK cells. Following pCMV injections, SJL/J mice were infected with TMEV or challenged with encephalitogenic myelin proteolipid protein (PLP) peptides. pCMV injection exacerbated TMEV-induced demyelinating disease in a dose-dependent manner. Exacerbation of the disease did not correlate with the number of TMEV-antigen positive cells but did with an increase in anti-TMEV antibody. pCMV injection also enhanced R-EAE with increased IFNgamma and IL-6 responses. These results caution the use of DNA vaccination in MS patients and other possible Th1-mediated diseases.
Insights
Plasmid DNA (pCMV) can stimulate immune responses, potentially worsening multiple sclerosis (MS) models. This suggests caution when using DNA vaccination for MS and other Th1-mediated diseases.
Area of Science:
- Immunology
- Neuroscience
- Virology
Background:
- Multiple sclerosis (MS) etiology is investigated using viral (Theiler's murine encephalomyelitis virus - TMEV) and autoimmune (relapsing-remitting experimental allergic encephalomyelitis - R-EAE) models.
- DNA immunization is a novel vaccination strategy with a reported low incidence of adverse effects.
- Bacterial DNA containing CpG motifs is known to enhance immunostimulation.
Purpose of the Study:
- To determine if plasmid DNA (pCMV), a common DNA immunization vector, causes immunostimulation in vitro.
- To evaluate the effect of pCMV injection on animal models of MS in vivo.
Main Methods:
- In vitro assessment of pCMV's ability to induce cytokine production (IL-12, IFNgamma, IL-6) and NK cell activation.
- In vivo studies involving SJL/J mice infected with TMEV or challenged with myelin proteolipid protein (PLP) peptides after pCMV injection.
Main Results:
- pCMV induced Th1-promoting cytokines (IL-12, IFNgamma) and IL-6, and activated NK cells in vitro.
- pCMV injection exacerbated TMEV-induced demyelinating disease in a dose-dependent manner, correlating with increased anti-TMEV antibodies.
- pCMV enhanced R-EAE, accompanied by increased IFNgamma and IL-6 responses.
Conclusions:
- Bacterially derived plasmid DNA (pCMV) possesses immunostimulatory properties.
- pCMV administration can worsen animal models of MS, suggesting potential risks for MS patients.
- Caution is advised regarding the use of DNA vaccination in MS and other Th1-mediated diseases.