Pathologic inflammation and neuronal damage during murine neurocysticercosis associates with increased expression of IL-1β

Abstract

Abstract Neurocysticercosis (NCC) is the leading cause of acquired epilepsy worldwide caused by Taenia solium larvae. Disease progression involves an initial asymptomatic phase followed by a symptomatic period, in which dying organisms induce inflammation and symptoms such as seizures, intracranial hypertension, or cognitive decline. A mixed Th1/Th2 response develops in the brain, contrasting the canonical Th2 pathway associated with peripheral helminthic infections. We found that disease progression was more severe in BALB/c mice, correlating with increased parasite burdens and enhanced eosinophil and macrophage infiltration, although comparable numbers of T cells were detected. Moreover, elevated IL-1β levels were significantly elevated in BALB/c mice. Notably, Mrc1-deficient mice which exhibited a more resistant phenotype with decreased mortality and morbidity displayed low IL-1β expression. Therefore, we hypothesize that early up regulation of IL-1β in response to antigen recognition by macrophages plays a key role in damage to the nervous tissue. Comparison of glial and neuronal distribution in naïve and infected wild type C57BL6 and Balb/c mice, and also in strains with defective trafficking of eosinophils to the CNS, revealed that expression of IL-1β was detected early during infection and dramatically increased by 2 wks, colocalizing to macrophages and astrocytes. Notably, calbindin+ neurons were also significantly reduced in cerebellar regions where severe pockets of inflammatory cells are detected. Thus, our results suggest that IL-1β is a central proinflammatory mediator with neurotoxic potential during NCC infection.