Low responsiveness of peripheral lymphocytes in extraparenchymal neurocysticercosis

Abstract

Background The morbidity and mortality of extraparenchymal neurocysticercosis (EP-NC) remain high and effectiveness of current medical treatment is suboptimal. Various factors have been implicated in the severity of EP-NC and in the poor response to treatment, but the possible role of host immune and endocrine systems has not yet been examined thoroughly. Methodology/Principal findings 42 participants with EP-NC before receiving standard treatment and 25 healthy controls were included in the study. Treatment response was assessed by comparing pre/post treatment parasite volumes from 3D MRI. Prior to treatment among participants with EP-NC, specific stimulation induced an increased specific proliferative response accompanied by a significant increase in IL-4, NK, NKT, Bregs and Tregs cells, whereas in healthy controls, specific stimulation induced a significant increase in IL-1β, IL-5, CCL5, IL-6, TNF-α, NK and Bregs cells. Significant differences between participants with EP-NC and healthy controls in the specific inflammatory response were observed. Participants with EP-NC prior to treatment had significantly weaker responses of proinflammatory cytokines (IL-6, TNF-α) and NK cells, and stronger IL-4 response. Anthelmintic treatment did not promote significant peripheral immunological changes at any time, although inflammation was sustained in the cerebrospinal fluid. Serum estradiol concentration significantly decreased after anthelmintic treatment among males, and cortisol correlated negatively with IL-6 and positively with IFN-γ levels. No pre-treatment immunologic or endocrinologic parameters were significantly associated with response to treatment. Conclusion/Significance Prior to anthelmintic treatment, EP-NC was characterized by low lymphocyte reactivity accompanied by a regulatory response, which may be involved in the lack of peripheral immunological changes during and after treatment, although a central inflammatory response was present. This weak specific peripheral response could favor the chronicity of the infection and the poor response to treatment. Our findings highlight the need for new anti-inflammatory treatment focused on the central nervous system with less systemic immunosuppressive effects.

Can sPD-1 and sPD-L1 Plasma Concentrations Predict Treatment Response among Patients with Extraparenchymal Neurocysticercosis?

“…We also found several negative correlations between pre- and 1 month post-treatment concentrations of sPD-1 or sPD-L1 or their ratio and components of the inflammatory reaction (cytokines and cells). This association was previously shown in other contexts [ 16 ], and although in a previous study we did not find statistically significant associations between cytokine concentrations and response to treatment [ 5 ], these results may be related to the depressed immune status of these patients with severe disease and could contribute to the chronicity of the disease.…”

“…The patients included were a subgroup of those included in previous studies [ 3 , 5 ] and the reason why only a subgroup was included was due to the limited availability of plasma. Recruitment and general characteristics of the study population have been previously described [ 3 , 5 ].…”

“…The patients included were a subgroup of those included in previous studies [ 3 , 5 ] and the reason why only a subgroup was included was due to the limited availability of plasma. Recruitment and general characteristics of the study population have been previously described [ 3 , 5 ]. Briefly, a group of 21 patients with confirmed EP-NC [ 12 ] were included prior to the administration of a standard regimen of anthelmintic treatment (albendazole) plus corticosteroids and followed for at least 6 months to evaluate their responses to treatment via 3D-MRI to estimate the parasite volumes.…”

“…The cytokine titration and the evaluation of the specific peripheral immunologic profile were performed as described previously [ 5 ]. Briefly, the pro- and anti-inflammatory human cytokines IL-1β, IL-4, IL-5, IL-6, IL-17A, CCL5, and INF-γ (all from BioLegend, San Diego, CA, USA) were determined with commercial sandwich enzyme linked immunosorbent assay (ELISA) kits, following the supplier’s instructions.…”

“…We previously found that EP-NC occurs with a concomitant depressed reactivity to parasitic antigens, an increased CD25(high)Foxp3+ Treg differentiation, and a higher DC expression of the regulatory molecules signaling lymphocytic activation molecule family 1 (SLAMF1) and CD205, favoring a suppressive environment [ 4 , 5 ]. Specific stimulation of PBMCs from these patients does not induce the production of inflammatory cytokines (IL-5, IL-6, TNF-a), whereas this is the case in healthy controls [ 5 ]. Furthermore, some studies have highlighted the role of the pro-inflammatory response in the response to specific treatment of these EP-NC patients [ 6 ].…”