Systemic Escherichia coli infection does not influence clinical symptoms and neurodegeneration in experimental autoimmune encephalomyelitis

Abstract

Background: Systemic 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. Methods: Rats 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. Results: Systemic 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. Conclusions: We 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.