TY - JOUR
T1 - In vitro model of postoncosphere development, and in vivo infection abilities of Taenia solium and Taenia saginata
AU - for the Cysticercosis Working Group in Peru
AU - Palma, Sandra
AU - Chile, Nancy
AU - Carmen-Orozco, Rogger P.
AU - Trompeter, Grace
AU - Fishbeck, Kayla
AU - Cooper, Virginia
AU - Rapoport, Laura
AU - Bernal-Teran, Edson G.
AU - Condori, Beth J.
AU - Gilman, Robert H.
AU - Verastegui, Manuela R.
N1 - Funding Information:
This work was supported by NIH grant 5D43TW006581, Infectious Diseases Training Program in Peru (RHG), http://grantome.com/grant/NIH/D43-TW006581-05; Doctoral grant of the Franco-Peruvian School of Life Science, contrato 250-2015-FONDECYT - CONCYTEC (NC), www.cienciactiva.gob.pe; Convenio N°118-2015-FONDECYT - CONCYTEC (MRV), www.cienciactiva.gob.pe; and NIH grants U19AI129909 (HHG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Iskra Tuero and Yanina Arana for suggestions and technical assistance. Cysticercosis Working Group in Peru: Members of the CWGP include: Robert H. Gilman, MD, DTMH; Armando E. Gonzalez, DVM, PhD, Hector H. Garcia, MD (Coordination Board); Herbert Saavedra, MD; Manuel Martinez, MD; Isidro Gonzalez, MD (Instituto Nacional de Ciencias Neurológicas, Lima, Perú); Manuela Verastegui, PhD; Mirko Zimic, PhD; Javier Bustos, MD, MPH; Holger Mayta, PhD (Universidad Peruana Cayetano Heredia, Lima, Perú); Cesar M. Gavidia, DVM, PhD (School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos), Theodore E. Nash, MD; Siddhartha Mahanty, MD, PhD (NIAID, NIH, Bethesda, MD); Jonh Noh, BS, Sukwan Handali, MD (CDC, Atlanta, GA); Jon Friedland (Imperial College, London, UK).
Publisher Copyright:
© 2019 Palma et al.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pntd.0007261
DO - 10.1371/journal.pntd.0007261
M3 - Article
C2 - 30870421
AN - SCOPUS:85063951711
SN - 1935-2727
VL - 13
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 3
M1 - e0007261
ER -