Dataset Information

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

ABSTRACT:

Background

The 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.

Methodology

Peripheral 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 findings

Sera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-?/IL-12) and Th2 (IL-4/IL-13) cytokine responses and trends towards higher levels of IL-1?/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-? 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.

SUBMITTER: Tuero I

PROVIDER: S-EPMC4624727 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Tuero Iskra I Palma Sandra S Cabeza Franco F Saleemi Sarah S Rodriguez Silvia S Gonzales Isidro I Mayta Holger H Mahanty Siddhartha S Garcia Hector H HH Gilman Robert H RH

PLoS neglected tropical diseases 20151027 10

<h4>Background</h4>The 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.<h4>Methodology</h4>Peripheral blood mononuclear cells (PBMC) were obtained from untreated patients with neurocysticercosis (NCC), categorized as having parenchymal or subarachnoid infection by the presence of cysts exclu ...[more]

PMID: 26506532

Similar Datasets

Project description:BackgroundEstimating the burden of neglected tropical diseases is a valuable tool to support policymakers in the resource allocation for control and elimination of these diseases. Spatial analysis allows to identify the geographical distribution patterns of infectious and parasitic diseases within a country and allows to assess their possible correlation with other health disorders. Despite being neurocysticercosis (NCC) considered as the most important parasitic disease of the nervous system, few efforts have been addressed to assess the real burden of NCC in endemic countries, to date, there are no studies estimating the burden of NCC in South America. In this study we aimed to use the Disability Adjust Life Years (DALY) and spatial indicators as tools to measure the impact of human neurocysticercosis in Ecuador between 2013 and 2017.MethodsMortality, morbidity and spatial data from the national agency of statistics were used to estimate the burden of disease of NCC during a five-year period (2013-2017). NCC cases and its two main sequelae, epilepsy and migraine headache, were stratified by sex and age group to calculate the DALY associated to NCC using the DALY package in R. SATSCAN software was used to assess spatial clusters of NCC and its possible neurological sequelae as epilepsy, status epilepticus, migraine and hydrocephalus.Principal findingsThe burden of human neurocysticercosis ranged from 56201 [95% CI 29961-89333] to 59612 [95% CI 31854-94689] DALY per year, corresponding to 3.54 to 3.56 DALY per 1000 population. Average yearly incidence rates per 10 000 person-years were 0.23 [95% CI 0.21-0.26] for NCC, 4.89 [95% CI 4.78-5.00] for epilepsy, 0.130 [95% CI 0.11-0.15] for status epilepticus, 0.62 [95% CI 0.58-0.66] for migraine headache, and 1.02 [95% CI 0.98-1.07] for hydrocephalus. Most important significant spatial clusters (p<0.0001) were located in the southern region of the highlands of the country.Conclusion/significanceThis is the first study in South America to calculate estimates for burden of NCC and one of the few using spatial analysis to show the importance of sequelae other than epilepsy that play an important role in the impact of human neurocysticercosis.

Project description:BackgroundAntigen tests for diagnosis and disease monitoring in some types of neurocysticercosis (NCC) are useful but access to testing has been limited by availability of proprietary reagents and/or kits.Methods/principal findingsThree previously identified IgM-secreting hybridomas whose IgM products demonstrated specificity to Taenia solium underwent variable heavy and light chain sequencing and isotype conversion to mouse IgG. Screening of these recombinantly expressed IgG anti-Ts hybridomas, identified one (TsG10) with the highest affinity to crude Taenia antigen. TsG10 was then used as a capture antibody in a sandwich antigen detection immunoassay in combination with either a high titer polyclonal anti-Ts antibody or with biotinylated TsG10 (termed TsG10*bt). Using serum, plasma, and CSF samples from patients with active NCC and those from NCC-uninfected patients, ROC curve analyses demonstrated that the TsG10-TsG10-*bt assay achieved a 98% sensitivity and 100% specificity in detecting samples known to be antigen positive and outperformed the polyclonal based assay (sensitivity of 93% with 100% specificity). By comparing levels of Ts antigen (Ag) in paired CSF (n = 10) or plasma/serum (n = 19) samples from well-characterized patients with extra-parenchymal NCC early in infection and at the time of definitive cure, all but 2 (1 from CSF and 1 from plasma) became undetectable. There was a high degree of correlation (r = 0.98) between the Ag levels detected by this new assay and levels found by a commercial assay. Pilot studies indicate that this antigen can be detected in the urine of patients with active NCC.Conclusions/significanceA newly developed recombinant monoclonal antibody-based Ts Ag detection immunoassay is extremely sensitive in the detection of extra-parenchymal NCC and can be used to monitor the success of treatment in the CSF, serum/plasma and urine. The ability to produce recombinant TsG10 at scale should enable use of this antigen detection immunoassay wherever NCC is endemic.Clinical trial registrationClinicalTrials.gov Identifiers: NCT00001205 - & NCT00001645.

Dataset Information

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

Background

Methodology

Principal findings

Conclusions/significance

Publications

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

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