Abstract
BackgroundSystemic infections can influence the course of multiple sclerosis (MS), especially by driving recurrent acute episodes. The question whether the infection enhances tissue damage is of great clinical importance and cannot easily be assessed in clinical trials. Here, we investigated the effects of a systemic infection with Escherichia coli, a Gram-negative bacterium frequently causing urinary tract infections, on the clinical course as well as on neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS.MethodsRats were immunized with myelin oligodendrocyte glycoprotein (MOG1–125) and challenged intraperitoneally with live E. coli K1 in the preclinical or in the clinical phase of the disease. To ensure the survival of animals, antibiotic treatment with ceftriaxone was initiated 36 h after the infection and continued for 3 consecutive days.ResultsSystemic infection with E. coli did not influence the onset of clinical EAE symptoms or disease severity. Analysis of the optic nerve and retinal ganglion cells revealed no significant changes in the extent of inflammatory infiltrates, demyelination and neurodegeneration after E. coli infection.ConclusionsWe could not confirm the detrimental effect of lipopolysaccharide-induced systemic inflammation, a model frequently used to mimic the bacterial infection, previously observed in animal models of MS. Our results indicate that the effect of an acute E. coli infection on the course of MS is less pronounced than suspected and underline the need for adequate models to test the role of systemic infections in the pathogenesis of MS.
Highlights
Systemic infections can influence the course of multiple sclerosis (MS), especially by driving recurrent acute episodes
We investigated the impact of a systemic E. coli infection during the preclinical and clinical phase of experimental autoimmune encephalomyelitis (EAE), an animal model of MS induced by immunization with myelin oligodendrocyte glycoprotein (MOG) in female Brown Norway rats, which shows a progressive disease course without any definite form of remission
We have previously demonstrated that this model strongly reflects the neurodegenerative aspects of MS. 12–14 days after immunization with MOG, more than 90% of affected animals develop acute optic neuritis, which leads to acute axonal degeneration of the optic nerve and consecutive apoptosis of retinal ganglion cells (RGCs) [17,18,19]
Summary
Systemic infections can influence the course of multiple sclerosis (MS), especially by driving recurrent acute episodes. We investigated the effects of a systemic infection with Escherichia coli, a Gram-negative bacterium frequently causing urinary tract infections, on the clinical course as well as on neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Few studies in humans or animal models demonstrated an exacerbating effect of an acute infection with Gram-negative bacteria on the disease course of MS and EAE [13,14,15]. We investigated the impact of a systemic E. coli infection during the preclinical and clinical phase of experimental autoimmune encephalomyelitis (EAE), an animal model of MS induced by immunization with myelin oligodendrocyte glycoprotein (MOG) in female Brown Norway rats, which shows a progressive disease course without any definite form of remission. The amount of spinal cord lesions shows certain variability in this model [20,21,22]
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