Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine?
BACKGROUND:Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased...
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ftdoajarticles:oai:doaj.org/article:eb21b9736c534873b3d4c0dfcff0c4e3 2023-05-15T15:14:36+02:00 Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine? Xiao-Hong Li Yu-Xin Xu Gill Vance Yun Wang Long-Bao Lv Govert J van Dam Jian-Ping Cao R Alan Wilson 2015-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003925 https://doaj.org/article/eb21b9736c534873b3d4c0dfcff0c4e3 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4498593?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003925 https://doaj.org/article/eb21b9736c534873b3d4c0dfcff0c4e3 PLoS Neglected Tropical Diseases, Vol 9, Iss 7, p e0003925 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003925 2022-12-31T03:54:49Z BACKGROUND:Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes. METHODOLOGY/PRINCIPAL FINDINGS:We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function. CONCLUSIONS/SIGNIFICANCE:Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 7 e0003925 |
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English |
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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 Xiao-Hong Li Yu-Xin Xu Gill Vance Yun Wang Long-Bao Lv Govert J van Dam Jian-Ping Cao R Alan Wilson Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine? |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes. METHODOLOGY/PRINCIPAL FINDINGS:We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function. CONCLUSIONS/SIGNIFICANCE:Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets. |
format |
Article in Journal/Newspaper |
author |
Xiao-Hong Li Yu-Xin Xu Gill Vance Yun Wang Long-Bao Lv Govert J van Dam Jian-Ping Cao R Alan Wilson |
author_facet |
Xiao-Hong Li Yu-Xin Xu Gill Vance Yun Wang Long-Bao Lv Govert J van Dam Jian-Ping Cao R Alan Wilson |
author_sort |
Xiao-Hong Li |
title |
Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine? |
title_short |
Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine? |
title_full |
Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine? |
title_fullStr |
Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine? |
title_full_unstemmed |
Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine? |
title_sort |
evidence that rhesus macaques self-cure from a schistosoma japonicum infection by disrupting worm esophageal function: a new route to an effective vaccine? |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0003925 https://doaj.org/article/eb21b9736c534873b3d4c0dfcff0c4e3 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 7, p e0003925 (2015) |
op_relation |
http://europepmc.org/articles/PMC4498593?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003925 https://doaj.org/article/eb21b9736c534873b3d4c0dfcff0c4e3 |
op_doi |
https://doi.org/10.1371/journal.pntd.0003925 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
7 |
container_start_page |
e0003925 |
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