Related Experiment Videos
Treatment with bacterial LPS renders genetically resistant C57BL/6 mice susceptible to Theiler's virus-induced
L C Pullen1, S H Park, S D Miller
1Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
Abstract:
Theiler's murine encephalomyelitis virus (TMEV) induces a demyelinating disease in susceptible strains, which clinically and histopathologically resembles human multiple sclerosis. Since bacterial LPS produced by Gram-negative bacteria is known to potentiate an immune response and trigger resident central nervous system cells to produce various inflammatory cytokines, we examined the ability of LPS to affect resistance to TMEV-induced demyelinating disease (TMEV-IDD). Intraperitoneal injection of LPS, concomitant with intracerebral of genetically resistant C57BL/6 mice with TMEV, resulted in clinical symptoms in approximately 50% of the group. The increase in susceptibility following LPS treatment correlated with the enhanced levels of TMEV-specific delayed-type hypersensitivity and T cell proliferative responses. Similar treatment with LPS, however, did not accelerate the clinical course of susceptible (SJL/J) or intermediately susceptible (C3H) mice. The LPS-treated C57BL/6 mice displayed an increased viral persistence in the central nervous system when compared with nontreated control mice. Intraperitoneal administration of IL-1 beta could mimic the LPS effect in C57BL/6 mice, suggesting that the increase in susceptibility to TMEV-IDD may function via IL-1 produced following LPS stimulation.
Insights
Bacterial lipopolysaccharide (LPS) increases susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) in resistant mice by enhancing immune responses and viral persistence. Interleukin-1 beta (IL-1 beta) may mediate this LPS effect.
Area of Science:
- Neuroimmunology
- Virology
- Infectious Diseases
Background:
- Theiler's murine encephalomyelitis virus (TMEV) infection causes demyelination, mimicking human multiple sclerosis.
- Bacterial lipopolysaccharide (LPS) is known to potentiate immune responses and induce cytokine production in the central nervous system.
Purpose of the Study:
- To investigate the effect of LPS on resistance to TMEV-induced demyelinating disease (TMEV-IDD).
- To explore the role of immune responses and viral persistence in LPS-mediated susceptibility.
- To determine the potential involvement of Interleukin-1 beta (IL-1 beta) in the observed effects.
Main Methods:
- Genetically resistant C57BL/6 mice were intracerebrally inoculated with TMEV and intraperitoneally injected with LPS.
- Immune responses, including delayed-type hypersensitivity and T cell proliferation, were assessed.
- Viral persistence in the central nervous system was measured.
- The effect of IL-1 beta administration was evaluated.
Main Results:
- LPS treatment rendered genetically resistant C57BL/6 mice susceptible to TMEV-IDD, with clinical symptoms in approximately 50% of the group.
- LPS-treated mice showed enhanced TMEV-specific delayed-type hypersensitivity and T cell proliferation, along with increased viral persistence in the CNS.
- LPS did not accelerate disease in susceptible (SJL/J) or intermediately susceptible (C3H) mice.
- Intraperitoneal administration of IL-1 beta mimicked the LPS effect in C57BL/6 mice.
Conclusions:
- Bacterial LPS can overcome genetic resistance to TMEV-induced demyelinating disease in mice.
- This increased susceptibility is associated with enhanced TMEV-specific immune responses and increased viral persistence.
- IL-1 beta may be a key mediator of LPS-induced susceptibility to TMEV-IDD.