The interaction of classical complement component C1 with parasite and host calreticulin mediates Trypanosoma cruzi infection of human placenta.
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 i...
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ftdoajarticles:oai:doaj.org/article:e1aa1daf910e4202b11f5fef1c7c6752 2023-05-15T15:14:21+02:00 The interaction of classical complement component C1 with parasite and host calreticulin mediates Trypanosoma cruzi infection of human placenta. Christian Castillo Galia Ramírez Carolina Valck Lorena Aguilar Ismael Maldonado Carlos Rosas Norbel Galanti Ulrike Kemmerling Arturo Ferreira 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002376 https://doaj.org/article/e1aa1daf910e4202b11f5fef1c7c6752 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3749977?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002376 https://doaj.org/article/e1aa1daf910e4202b11f5fef1c7c6752 PLoS Neglected Tropical Diseases, Vol 7, Iss 8, p e2376 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002376 2022-12-31T01:33:07Z 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 ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Canada PLoS Neglected Tropical Diseases 7 8 e2376 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Christian Castillo Galia Ramírez Carolina Valck Lorena Aguilar Ismael Maldonado Carlos Rosas Norbel Galanti Ulrike Kemmerling Arturo Ferreira The interaction of classical complement component C1 with parasite and host calreticulin mediates Trypanosoma cruzi infection of human placenta. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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 ... |
format |
Article in Journal/Newspaper |
author |
Christian Castillo Galia Ramírez Carolina Valck Lorena Aguilar Ismael Maldonado Carlos Rosas Norbel Galanti Ulrike Kemmerling Arturo Ferreira |
author_facet |
Christian Castillo Galia Ramírez Carolina Valck Lorena Aguilar Ismael Maldonado Carlos Rosas Norbel Galanti Ulrike Kemmerling Arturo Ferreira |
author_sort |
Christian Castillo |
title |
The interaction of classical complement component C1 with parasite and host calreticulin mediates Trypanosoma cruzi infection of human placenta. |
title_short |
The interaction of classical complement component C1 with parasite and host calreticulin mediates Trypanosoma cruzi infection of human placenta. |
title_full |
The interaction of classical complement component C1 with parasite and host calreticulin mediates Trypanosoma cruzi infection of human placenta. |
title_fullStr |
The interaction of classical complement component C1 with parasite and host calreticulin mediates Trypanosoma cruzi infection of human placenta. |
title_full_unstemmed |
The interaction of classical complement component C1 with parasite and host calreticulin mediates Trypanosoma cruzi infection of human placenta. |
title_sort |
interaction of classical complement component c1 with parasite and host calreticulin mediates trypanosoma cruzi infection of human placenta. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002376 https://doaj.org/article/e1aa1daf910e4202b11f5fef1c7c6752 |
geographic |
Arctic Canada |
geographic_facet |
Arctic Canada |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 8, p e2376 (2013) |
op_relation |
http://europepmc.org/articles/PMC3749977?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002376 https://doaj.org/article/e1aa1daf910e4202b11f5fef1c7c6752 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002376 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
7 |
container_issue |
8 |
container_start_page |
e2376 |
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1766344813003669504 |