The Experts below are selected from a list of 63 Experts worldwide ranked by ideXlab platform
Arturo Ferreira - One of the best experts on this subject based on the ideXlab platform.
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exogenous calreticulin incorporated onto non infective trypanosoma cruzi epimastigotes promotes their internalization into mammal host cells
Immunobiology, 2017Co-Authors: Eduardo Sosoniukroche, Carolina Valck, Carlos Rosas, Gerardo Vallejos, Lorena Aguilarguzman, Javier Pizarrobauerle, Katherine Weinberger, Marek Michalak, Arturo FerreiraAbstract:Abstract Chagas disease is an endemic pathology in Latin America, now emerging in developed countries, caused by the intracellular protozoan Trypanosoma cruzi , whose life cycle involves three stages: amastigotes, epimastigotes, and trypomastigotes. T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum resident chaperone, translocates to the external cellular membrane, where it captures Complement Component C1, ficolins and MBL, thus inactivating the classical and lectin pathways. Trypomastigote-bound C1 is detected as an “eat me” signal by macrophages and promotes the infective process. Unlike infective trypomastigotes, non-infective epimastigotes either do not express or express only marginal levels of TcCRT on their external membrane. We show that epimastigotes bind exogenous rTcCRT to their cellular membrane and, in the presence of C1q, this parasite form is internalized into normal fibroblasts. On the other hand, Calreticulin (CRT)-deficient fibroblasts show impaired parasite internalization. In synthesis, CRT from both parasite and host cell origin is important in the establishment of C1q-dependent first contacts between parasites and host cells.
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the interaction of classical Complement Component C1 with parasite and host calreticulin mediates trypanosoma cruzi infection of human placenta
PLOS Neglected Tropical Diseases, 2013Co-Authors: Christian Castillo, Galia Ramirez, Carolina Valck, Lorena Aguilar, Ismael Maldonado, Carlos Rosas, Norbel Galanti, Ulrike Kemmerling, Arturo FerreiraAbstract:Background 9 million people are infected with Trypanosoma cruzi in Latin America, plus more than 300,000 in the United States, Canada, Europe, Australia, and Japan. Approximately 30% of infected individuals develop circulatory or digestive pathology. While in underdeveloped countries transmission is mainly through hematophagous arthropods, transplacental infection prevails in developed ones. Methodology/Principal Findings During infection, T. cruzi calreticulin (TcCRT) translocates from the endoplasmic reticulum to the area of flagellum emergence. There, TcCRT acts as virulence factor since it binds maternal classical Complement Component C1q that recognizes human calreticulin (HuCRT) in placenta, with increased parasite infectivity. As measured ex vivo by quantitative PCR in human placenta chorionic villi explants (HPCVE) (the closest available correlate of human congenital T. cruzi infection), C1q mediated up to a 3–5-fold increase in parasite load. Because anti-TcCRT and anti-HuCRT F(ab′)2 antibody fragments are devoid of their Fc-dependent capacity to recruit C1q, they reverted the C1q-mediated increase in parasite load by respectively preventing its interaction with cell-bound CRTs from both parasite and HPCVE origins. The use of competing fluid-phase recombinant HuCRT and F(ab′)2 antibody fragments anti-TcCRT corroborated this. These results are consistent with a high expression of fetal CRT on placental free chorionic villi. Increased C1q-mediated infection is paralleled by placental tissue damage, as evidenced by histopathology, a damage that is ameliorated by anti-TcCRT F(ab′)2 antibody fragments or fluid-phase HuCRT. Conclusions/Significance T. cruzi infection of HPCVE is importantly mediated by human and parasite CRTs and C1q. Most likely, C1q bridges CRT on the parasite surface with its receptor orthologue on human placental cells, thus facilitating the first encounter between the parasite and the fetal derived placental tissue. The results presented here have several potential translational medicine aspects, specifically related with the capacity of antibody fragments to inhibit the C1q/CRT interactions and thus T. cruzi infectivity.
Carolina Valck - One of the best experts on this subject based on the ideXlab platform.
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exogenous calreticulin incorporated onto non infective trypanosoma cruzi epimastigotes promotes their internalization into mammal host cells
Immunobiology, 2017Co-Authors: Eduardo Sosoniukroche, Carolina Valck, Carlos Rosas, Gerardo Vallejos, Lorena Aguilarguzman, Javier Pizarrobauerle, Katherine Weinberger, Marek Michalak, Arturo FerreiraAbstract:Abstract Chagas disease is an endemic pathology in Latin America, now emerging in developed countries, caused by the intracellular protozoan Trypanosoma cruzi , whose life cycle involves three stages: amastigotes, epimastigotes, and trypomastigotes. T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum resident chaperone, translocates to the external cellular membrane, where it captures Complement Component C1, ficolins and MBL, thus inactivating the classical and lectin pathways. Trypomastigote-bound C1 is detected as an “eat me” signal by macrophages and promotes the infective process. Unlike infective trypomastigotes, non-infective epimastigotes either do not express or express only marginal levels of TcCRT on their external membrane. We show that epimastigotes bind exogenous rTcCRT to their cellular membrane and, in the presence of C1q, this parasite form is internalized into normal fibroblasts. On the other hand, Calreticulin (CRT)-deficient fibroblasts show impaired parasite internalization. In synthesis, CRT from both parasite and host cell origin is important in the establishment of C1q-dependent first contacts between parasites and host cells.
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the interaction of classical Complement Component C1 with parasite and host calreticulin mediates trypanosoma cruzi infection of human placenta
PLOS Neglected Tropical Diseases, 2013Co-Authors: Christian Castillo, Galia Ramirez, Carolina Valck, Lorena Aguilar, Ismael Maldonado, Carlos Rosas, Norbel Galanti, Ulrike Kemmerling, Arturo FerreiraAbstract:Background 9 million people are infected with Trypanosoma cruzi in Latin America, plus more than 300,000 in the United States, Canada, Europe, Australia, and Japan. Approximately 30% of infected individuals develop circulatory or digestive pathology. While in underdeveloped countries transmission is mainly through hematophagous arthropods, transplacental infection prevails in developed ones. Methodology/Principal Findings During infection, T. cruzi calreticulin (TcCRT) translocates from the endoplasmic reticulum to the area of flagellum emergence. There, TcCRT acts as virulence factor since it binds maternal classical Complement Component C1q that recognizes human calreticulin (HuCRT) in placenta, with increased parasite infectivity. As measured ex vivo by quantitative PCR in human placenta chorionic villi explants (HPCVE) (the closest available correlate of human congenital T. cruzi infection), C1q mediated up to a 3–5-fold increase in parasite load. Because anti-TcCRT and anti-HuCRT F(ab′)2 antibody fragments are devoid of their Fc-dependent capacity to recruit C1q, they reverted the C1q-mediated increase in parasite load by respectively preventing its interaction with cell-bound CRTs from both parasite and HPCVE origins. The use of competing fluid-phase recombinant HuCRT and F(ab′)2 antibody fragments anti-TcCRT corroborated this. These results are consistent with a high expression of fetal CRT on placental free chorionic villi. Increased C1q-mediated infection is paralleled by placental tissue damage, as evidenced by histopathology, a damage that is ameliorated by anti-TcCRT F(ab′)2 antibody fragments or fluid-phase HuCRT. Conclusions/Significance T. cruzi infection of HPCVE is importantly mediated by human and parasite CRTs and C1q. Most likely, C1q bridges CRT on the parasite surface with its receptor orthologue on human placental cells, thus facilitating the first encounter between the parasite and the fetal derived placental tissue. The results presented here have several potential translational medicine aspects, specifically related with the capacity of antibody fragments to inhibit the C1q/CRT interactions and thus T. cruzi infectivity.
Carlos Rosas - One of the best experts on this subject based on the ideXlab platform.
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exogenous calreticulin incorporated onto non infective trypanosoma cruzi epimastigotes promotes their internalization into mammal host cells
Immunobiology, 2017Co-Authors: Eduardo Sosoniukroche, Carolina Valck, Carlos Rosas, Gerardo Vallejos, Lorena Aguilarguzman, Javier Pizarrobauerle, Katherine Weinberger, Marek Michalak, Arturo FerreiraAbstract:Abstract Chagas disease is an endemic pathology in Latin America, now emerging in developed countries, caused by the intracellular protozoan Trypanosoma cruzi , whose life cycle involves three stages: amastigotes, epimastigotes, and trypomastigotes. T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum resident chaperone, translocates to the external cellular membrane, where it captures Complement Component C1, ficolins and MBL, thus inactivating the classical and lectin pathways. Trypomastigote-bound C1 is detected as an “eat me” signal by macrophages and promotes the infective process. Unlike infective trypomastigotes, non-infective epimastigotes either do not express or express only marginal levels of TcCRT on their external membrane. We show that epimastigotes bind exogenous rTcCRT to their cellular membrane and, in the presence of C1q, this parasite form is internalized into normal fibroblasts. On the other hand, Calreticulin (CRT)-deficient fibroblasts show impaired parasite internalization. In synthesis, CRT from both parasite and host cell origin is important in the establishment of C1q-dependent first contacts between parasites and host cells.
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the interaction of classical Complement Component C1 with parasite and host calreticulin mediates trypanosoma cruzi infection of human placenta
PLOS Neglected Tropical Diseases, 2013Co-Authors: Christian Castillo, Galia Ramirez, Carolina Valck, Lorena Aguilar, Ismael Maldonado, Carlos Rosas, Norbel Galanti, Ulrike Kemmerling, Arturo FerreiraAbstract:Background 9 million people are infected with Trypanosoma cruzi in Latin America, plus more than 300,000 in the United States, Canada, Europe, Australia, and Japan. Approximately 30% of infected individuals develop circulatory or digestive pathology. While in underdeveloped countries transmission is mainly through hematophagous arthropods, transplacental infection prevails in developed ones. Methodology/Principal Findings During infection, T. cruzi calreticulin (TcCRT) translocates from the endoplasmic reticulum to the area of flagellum emergence. There, TcCRT acts as virulence factor since it binds maternal classical Complement Component C1q that recognizes human calreticulin (HuCRT) in placenta, with increased parasite infectivity. As measured ex vivo by quantitative PCR in human placenta chorionic villi explants (HPCVE) (the closest available correlate of human congenital T. cruzi infection), C1q mediated up to a 3–5-fold increase in parasite load. Because anti-TcCRT and anti-HuCRT F(ab′)2 antibody fragments are devoid of their Fc-dependent capacity to recruit C1q, they reverted the C1q-mediated increase in parasite load by respectively preventing its interaction with cell-bound CRTs from both parasite and HPCVE origins. The use of competing fluid-phase recombinant HuCRT and F(ab′)2 antibody fragments anti-TcCRT corroborated this. These results are consistent with a high expression of fetal CRT on placental free chorionic villi. Increased C1q-mediated infection is paralleled by placental tissue damage, as evidenced by histopathology, a damage that is ameliorated by anti-TcCRT F(ab′)2 antibody fragments or fluid-phase HuCRT. Conclusions/Significance T. cruzi infection of HPCVE is importantly mediated by human and parasite CRTs and C1q. Most likely, C1q bridges CRT on the parasite surface with its receptor orthologue on human placental cells, thus facilitating the first encounter between the parasite and the fetal derived placental tissue. The results presented here have several potential translational medicine aspects, specifically related with the capacity of antibody fragments to inhibit the C1q/CRT interactions and thus T. cruzi infectivity.
Eduardo Sosoniukroche - One of the best experts on this subject based on the ideXlab platform.
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exogenous calreticulin incorporated onto non infective trypanosoma cruzi epimastigotes promotes their internalization into mammal host cells
Immunobiology, 2017Co-Authors: Eduardo Sosoniukroche, Carolina Valck, Carlos Rosas, Gerardo Vallejos, Lorena Aguilarguzman, Javier Pizarrobauerle, Katherine Weinberger, Marek Michalak, Arturo FerreiraAbstract:Abstract Chagas disease is an endemic pathology in Latin America, now emerging in developed countries, caused by the intracellular protozoan Trypanosoma cruzi , whose life cycle involves three stages: amastigotes, epimastigotes, and trypomastigotes. T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum resident chaperone, translocates to the external cellular membrane, where it captures Complement Component C1, ficolins and MBL, thus inactivating the classical and lectin pathways. Trypomastigote-bound C1 is detected as an “eat me” signal by macrophages and promotes the infective process. Unlike infective trypomastigotes, non-infective epimastigotes either do not express or express only marginal levels of TcCRT on their external membrane. We show that epimastigotes bind exogenous rTcCRT to their cellular membrane and, in the presence of C1q, this parasite form is internalized into normal fibroblasts. On the other hand, Calreticulin (CRT)-deficient fibroblasts show impaired parasite internalization. In synthesis, CRT from both parasite and host cell origin is important in the establishment of C1q-dependent first contacts between parasites and host cells.
Beverly L Trimpe - One of the best experts on this subject based on the ideXlab platform.
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C1 inhibitor different mechanisms of reaction with Complement Component C1 and C1s
Immunological Investigations, 1991Co-Authors: Glen L Hortin, Beverly L TrimpeAbstract:Inactivation of human Complement subComponent Cl¯s by its regulator C1 inhibitor at physiological ionic strength proceeded at a 3-fold higher rate when Cl¯s was in the physiological CT complex with subComponents C1q and Cl¯r rather than as a purified subunit. When the Cl¯ complex was disassembled by chelation of calcium, the Cl¯s subComponent was inactivated by C1 inhibitor at rates similar to those for the purified proteinase. Increasing ionic strength had little effect on the reaction of purified Cl¯s with C1 inhibitor but greatly diminished the rate of reaction of intact CT. Addition of heparin accelerated the inactivation of purified Cl¯s by Cl¯ inhibitor up to 25-fold but increased the inactivation of intact Cl¯ only about 5-fold. These differences in the inactivation of Cl¯s by Cl¯ inhibitor, depending on whether the proteinase is free or complexed with other subComponents of Cl¯, suggest different mechanisms of reaction. Occurrence of subComponent Cl¯s in a macromolecular complex with Cl¯q and Cl¯r...
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C1 inhibitor different mechanisms of reaction with Complement Component C1 and C1s
Immunological Investigations, 1991Co-Authors: Glen L Hortin, Beverly L TrimpeAbstract:Inactivation of human Complement subComponent C1-s by its regulator C1 inhibitor at physiological ionic strength proceeded at a 3-fold higher rate when C1-s was in the physiological C1- complex with subComponents C1q and C1-r rather than as purified subunit. When the C1- complex was disassembled by chelation of calcium, the C1-s subComponent was inactivated by C1 inhibitor at rates similar to those for the purified proteinase. Increasing ionic strength had little effect on the reaction of purified C1-s with C1 inhibitor but greatly diminished the rate of reaction of intact C1-. Addition of heparin accelerated the inactivation of purified C1-s by C1 inhibitor up to 25-fold but increased the inactivation of intact C1- only about 5-fold. These differences in the inactivation of C1-s by C1 inhibitor, depending on whether the proteinase is free or complexed with other subComponents of C1-, suggest different mechanisms of reaction. Occurrence of subComponent C1-s in a macromolecular complex with C1q and C1-r, thus, appears to be critical not only for directing its physiological activation but also its inactivation.