A Comparative Study of Peripheral Immune Responses to Taenia solium in Individuals with Parenchymal and Subarachnoid Neurocysticercosis

Abstract

BackgroundThe ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection.MethodologyPeripheral blood mononuclear cells (PBMC) were obtained from untreated patients with neurocysticercosis (NCC), categorized as having parenchymal or subarachnoid infection by the presence of cysts exclusively within the parenchyma or in subarachnoid spaces of the brain, and from uninfected (control) individuals matched by age and gender to each patient. Using multiplex detection technology, sera from NCC patients and controls and cytokine production by PBMC after T. solium antigen (TsAg) stimulation were assayed for levels of inflammatory and regulatory cytokines. PBMC were phenotyped by flow cytometry ex vivo and following in vitro stimulation with TsAg.Principal FindingsSera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-γ/IL-12) and Th2 (IL-4/IL-13) cytokine responses and trends towards higher levels of IL-1β/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-β secretion was detected in PBMC supernatants from parenchymal than in subarachnoid NCC. In contrast, there was a significantly higher IL-10 response to TsAg stimulation in patients with subarachnoid NCC compared to parenchymal NCC. Although no differences in regulatory T cells (Tregs) frequencies were found ex vivo, there was a trend towards greater expansion of Tregs upon TsAg stimulation in subarachnoid than in parenchymal NCC when data were normalized for the corresponding controls.Conclusions/Significance T. solium infection of the subarachnoid space is associated with an enhanced regulatory immune response compared to infection in the parenchyma. The resulting anti-inflammatory milieu may represent a parasite strategy to maintain a permissive environment in the host or diminish inflammatory damage from the host immune response in the central nervous system.

Regulation of the host immune system by helminth parasites

“…It is well recognized that pathologic inflammation can be dampened by immunoregulatory mechanisms that might underpin the asymptomatic phase of disease 25 . However, patients with the most highly disseminated infections actually show the greatest degree of immunoregulation, with increased IL-10 levels, decreased T H 1 and T H 2 cytokine levels, and a trend for increased Treg cell numbers 26 . Thus the immune response to T solium infection is finely poised: strong immunomodulation leads to dissemination of the parasite, whereas failure to regulate inflammation causes seizures and death.…”

Pathogenesis ofTaenia soliumtaeniasis and cysticercosis

“…At a cellular level, there is decreased lymphocytic proliferation, inhibition of granulocyte aggregation and chemotaxis, induction of Th2 response and suppression of prostaglandin E2‐mediated inflammation . Upregulation of Treg cell responses, both at the central and peripheral levels, is other mechanisms that have been recently revisited, particularly in subarachnoid NCC .…”

“…Evidently inflammation has a role in triggering seizures and other symptoms in parenchymal brain cysticercosis. Parenchymal NCC is associated with a peripheral proinflammatory cytokine profile mediated by IFN‐γ, IL‐12 y IL‐1β and neuroinflammation triggered by parasite products may damage perilesional brain parenchyma . Data from CT or MRI studies in patients attending clinical centres with live cysts show in most cases inflammation around at least one of the parasites .…”

“…Inflammatory mechanisms also contribute to alter CSF circulation, and subarachnoid NCC is associated with a profuse cellular response with increased proteins , and a strong inflammatory response with increased IL‐1β, IL‐6 and TNFα . Peripherally, there is a markedly increased regulatory T‐cell activity, likely as a mechanism of compensation to parasite‐driven inflammatory responses . Regulatory T cells (Treg) populations appear to be expanded in cysticercosis infections and likely play an important role in limiting the inflammatory response in the CNS by blocking inflammation through IL10 production and cell‐to‐cell contact with dendritic cells .…”

“…Peripherally, there is a markedly increased regulatory T‐cell activity, likely as a mechanism of compensation to parasite‐driven inflammatory responses . Regulatory T cells (Treg) populations appear to be expanded in cysticercosis infections and likely play an important role in limiting the inflammatory response in the CNS by blocking inflammation through IL10 production and cell‐to‐cell contact with dendritic cells . The development of granular ependymitis can contribute to narrowing or blockage of the aqueduct in patients with ventricular NCC .…”