High in vitro immune reactivity to Escherichia coli in neuromyelitis optica patients is correlated with both neurological disabilities and elevated plasma lipopolysaccharide levels

Abstract

The pathogenesis of neuromyelitis optica (NMO) is influenced by a combination of genetic and environmental factors, including infectious agents. Several infectious diseases can both trigger or exacerbate autoimmunity. The objective of the present work was to evaluate the in vitro immune responsiveness to Escherichia coli (EC), Staphylococcus aureus (SA) and Candida albicans (CA) in remittent-recurrent NMO patients, and correlate it with the level of neurological disability. Our results revealed that the extent of lymphoproliferation and cytokine profile in response to SA- and CA-stimulated PBMC cultures was similar between NMO patients and healthy individuals. Nevertheless, a higher in vitro CD4(+) T cell proliferation associated with elevated IL-1β, IL-6 and IL-17 release was observed in NMO-derived EC-stimulated cell cultures. Additionally, in these last cultures, the IL-10 production was significantly lower as compared with control group. The in vitro EC-induced levels of IL-6 and IL-17 were positively related with neurological disabilities. This higher tendency to produce Th17-related cytokines was proportional to the production of IL-23 and IL-6 by LPS-activated monocytes. Interestingly, elevated LPS levels were quantified in the plasma of NMO patients. The results suggest that a higher Th17-responsiveness to E. coli could be involved in the NMO pathogenesis.