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Racemose neurocysticercosis is an aggressive disease caused by the aberrant expansion of the cyst form of Taenia solium within the subarachnoid spaces of the human brain and spinal cord resulting in a mass effect and chronic inflammation. Although expansion is likely caused by the proliferation and growth of the parasite bladder wall, there is little direct evidence of the mechanisms that underlie these processes. Since the development and growth of cysts in related cestodes involves totipotential germinative cells, we hypothesized that the expansive growth of the racemose larvae is organized and maintained by germinative cells. Here, we identified proliferative cells expressing the serine/threonine-protein kinase plk1 by in situ hybridization. Proliferative cells were present within the bladder wall of racemose form and absent from the homologous tissue surrounding the vesicular form. Cyst proliferation in the related model species Taenia crassiceps (ORF strain) occurs normally by budding from the cyst bladder wall and proliferative cells were concentrated within the growth buds. Cells isolated from bladder wall of racemose larvae were established in primary cell culture and insulin stimulated their proliferation in a dose-dependent manner. These findings indicate that the growth of racemose larvae is likely due to abnormal cell proliferation. The different distribution of proliferative cells in the racemose larvae and their sensitivity to insulin may reflect significant changes at the cellular and molecular levels involved in their tumor-like growth. Parasite cell cultures offer a powerful tool to characterize the nature and formation of the racemose form, understand the developmental biology of T. solium, and to identify new effective drugs for treatment., Author summary Racemose neurocysticercosis is the most aggressive and lethal form of the disease characterized by progressive expansion of the larval stage of Taenia solium within the subarachnoid spaces of the brain. Currently, the cellular or molecular events that promote its formation and development are unknown. Our observations, employing tissue samples, revealed the presence of mitotically active cells in the bladder wall of the racemose larvae. Finally, we isolated and established primary cell cultures and observed that these cells are sensitive (proliferate in response to insulin). These results suggest that the proliferative cells stimulated by host biomolecules like hormones would be responsible for the abnormal growth of racemose larvae. Further studies are needed to identify all genes and pathways altered in the racemose form. The primary cell cultures will be used as a therapeutic target and allow us in future works to understand the developmental biology of the parasite.

Taenia solium is known to cause human cysticercosis while T. saginata does not. Comparative in vitro and in vivo studies on the oncosphere and the postoncospheral (PO) forms of T. solium and T. saginata may help to elucidate why cysticercosis can occur from one and not the other. The aim of this study was to use in vitro culture assays and in vivo models to study the differences in the development of the T. solium and T. saginata oncosphere. Furthermore, this study aimed to evaluate the expression of cytokines and metalloproteinases (MMPs) in human peripheral blood mononuclear cells (PBMCs), which were stimulated by these oncospheres and PO antigens. T. solium and T. saginata activated oncospheres (AO) were cultured in INT-407 and HCT-8 intestinal cells for 180 days. The T. solium began to die while the T. saginata grew for 180 days and developed to cysticerci in INT-407 cells. Rats were inoculated intracranially with AO and PO forms of either T. saginata or T. solium. Rats infected with T. solium AO and PO forms developed neurocysticercosis (NCC), while those infected with the T. saginata did not. Human PMBCs were stimulated with antigens of AO and PO forms of both species, and the production of cytokines and metalloproteinases (MMPs) was measured. The T. solium AO antigen stimulated a higher production of IL-4, IL-5, IL-13, IFN-γ, and IL-2 cytokines compared to T. saginata AO. In the PO form, the T. saginata PO antigen increased the production of IL-4, IL-5, IL-13, IFN-γ, IL-1β, IL-6, IL-10, TNF-α and IL-12 cytokines compared to T. solium, suggesting that this global immune response stimulated by different forms could permit survival or destruction of the parasite depending of their life-cycle stage. Regarding MMPs, T. solium AO antigen stimulated a higher production of MMP-9 compared to T. saginata AO antigen, which may be responsible for altering the permeability of intestinal cells and facilitating breakdown of the blood-brain barrier during the process of invasion of host tissue., Author summary Taenia solium and Taenia saginata are two parasites that cause the tissue infection cysticercosis in their intermediate hosts, pigs and cows, respectively. One major difference between them is that T. solium can also cause neurocysticercosis in the human brain, while T. saginata cannot. Neurocysticercosis is thought to be the major cause of adult-onset seizures in developing countries. It is not well understood why only T. solium can survive in human tissue; however, the host inflammatory response likely plays an important role. The authors found that human immune cells stimulated with T. solium in the early stages of the parasite life cycle produced a more robust cytokine response than T. saginata. However, in the mature stage, which occurs once T. solium reaches the brain, T. solium antigens stimulated a lower inflammatory response compared to T. saginata, suggesting the parasite is able to manipulate the host immune response in some way to evade destruction. These findings may support the differences in growth observed by the authors when rat brains were inoculated with either parasite species. This study provides new insights into the different ways T. solium and T. saginata activate the immune response to survive and develop within the host.

Background Serological tests have been used for the diagnosis of Taenia solium infection in pigs. However, those serological results do not necessarily correlate with the actual infection burden after performing pig necropsy. This study aimed to evaluate the Electro Immuno Transfer Blot (EITB) seropositivity with infection burden in naturally infected pigs. Methodology/Principal Findings In an endemic area of Peru, 476 pigs were sampled. Seroprevalence was 60.5±4.5% with a statistically higher proportion of positive older pigs (>8 months) than young pigs. The logistic model showed that pigs >8 month of age were 2.5 times more likely to be EITB-positive than ≤8 months. A subset of 84 seropositive pigs were necropsied, with 45.2% (38/84) positive to 1–2 bands, 46.4% (39/84) to 3 bands, and 8.3% (7/84) to 4+ bands. 41 out of 84 positive pigs were negative to necropsy (48.8%) and 43 (51%) had one or more cysts (positive predictive value). Older pigs showed more moderate and heavy infection burdens compared to younger pigs. In general, regardless of the age of the pig, the probability of having more cysts (parasite burden) increases proportionally with the number of EITB bands. Conclusions/Significance The probability of being necropsy-positive increased with the number of bands, and age. Therefore, the EITB is a measure of exposure rather than a test to determine the real prevalence of cysticercosis infection., Author Summary Taenia solium is a parasite that infects humans. The parasite eggs are released into the environment with human feces in villages with inadequate sanitation. Pigs might ingest the parasite eggs and develop the larval stage named cysticercosis (cysts), mainly in the muscles and heart. If a human accidentally ingests the parasite eggs, then the cysts develop principally in the central nervous system, a serious public health problem. Serological results in pigs do not always correlate with what is observed in the necropsy; in fact, some seropositive pigs are negative or have a few cysts. This study aimed to investigate the Electroimmunotransfer Blot (EITB) with the actual pig infection burden. We selected an endemic area of Peru, and sampled 476 pigs. Seroprevalence was 60.5% and there were more old positive pigs than young ones. A subset of 84 seropositive pigs were necropsied and only 43 (51%) had one or more cysts in the whole body. Older pigs also showed more moderate and heavy infection burdens compared to younger pigs. In general, the probability of having cysts increases with the number of EITB bands. This serological assay might be a measure of exposure rather than a test to detect the real disease.