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Co-ordinated Gene Expression in the Liver and Spleen during Schistosoma japonicum Infection Regulates Cell Migration
Determining the molecular events induced in the spleen during schistosome infection is an essential step in better understanding the immunopathogenesis of schistosomiasis and the mechanisms by which schistosomes modulate the host immune response. The present study defines the transcriptional and cel...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872641/ https://www.ncbi.nlm.nih.gov/pubmed/20502518 http://dx.doi.org/10.1371/journal.pntd.0000686 |
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author | Burke, Melissa L. McManus, Donald P. Ramm, Grant A. Duke, Mary Li, Yuesheng Jones, Malcolm K. Gobert, Geoffrey N. |
author_facet | Burke, Melissa L. McManus, Donald P. Ramm, Grant A. Duke, Mary Li, Yuesheng Jones, Malcolm K. Gobert, Geoffrey N. |
author_sort | Burke, Melissa L. |
collection | PubMed |
description | Determining the molecular events induced in the spleen during schistosome infection is an essential step in better understanding the immunopathogenesis of schistosomiasis and the mechanisms by which schistosomes modulate the host immune response. The present study defines the transcriptional and cellular events occurring in the murine spleen during the progression of Schistosoma japonicum infection. Additionally, we compared and contrasted these results with those we have previously reported for the liver. Microarray analysis combined with flow cytometry and histochemistry demonstrated that transcriptional changes occurring in the spleen were closely related to changes in cellular composition. Additionally, the presence of alternatively activated macrophages, as indicated by up-regulation of Chi3l3 and Chi3l4 and expansion of F4/80(+) macrophages, together with enhanced expression of the immunoregulatory genes ANXA1 and CAMP suggests the spleen may be an important site for the control of S. japonicum-induced immune responses. The most striking difference between the transcriptional profiles of the infected liver and spleen was the contrasting expression of chemokines and cell adhesion molecules. Lymphocyte chemokines, including the homeostatic chemokines CXCL13, CCL19 and CCL21, were significantly down-regulated in the spleen but up-regulated in the liver. Eosinophil (CCL11, CCL24), neutrophil (CXCL1) and monocyte (CXCL14, CCL12) chemokines and the cell adhesion molecules VCAM1, NCAM1, PECAM1 were up-regulated in the liver but unchanged in the spleen. Chemokines up-regulated in both organs were expressed at significantly higher levels in the liver. Co-ordinated expression of these genes probably contributes to the development of a chemotactic signalling gradient that promotes recruitment of effector cells to the liver, thereby facilitating the development of hepatic granulomas and fibrosis. Together these data provide, for the first time, a comprehensive overview of the molecular events occurring in the spleen during schistosomiasis and will substantially further our understanding of the local and systemic mechanisms driving the immunopathogenesis of this disease. |
format | Text |
id | pubmed-2872641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28726412010-05-25 Co-ordinated Gene Expression in the Liver and Spleen during Schistosoma japonicum Infection Regulates Cell Migration Burke, Melissa L. McManus, Donald P. Ramm, Grant A. Duke, Mary Li, Yuesheng Jones, Malcolm K. Gobert, Geoffrey N. PLoS Negl Trop Dis Research Article Determining the molecular events induced in the spleen during schistosome infection is an essential step in better understanding the immunopathogenesis of schistosomiasis and the mechanisms by which schistosomes modulate the host immune response. The present study defines the transcriptional and cellular events occurring in the murine spleen during the progression of Schistosoma japonicum infection. Additionally, we compared and contrasted these results with those we have previously reported for the liver. Microarray analysis combined with flow cytometry and histochemistry demonstrated that transcriptional changes occurring in the spleen were closely related to changes in cellular composition. Additionally, the presence of alternatively activated macrophages, as indicated by up-regulation of Chi3l3 and Chi3l4 and expansion of F4/80(+) macrophages, together with enhanced expression of the immunoregulatory genes ANXA1 and CAMP suggests the spleen may be an important site for the control of S. japonicum-induced immune responses. The most striking difference between the transcriptional profiles of the infected liver and spleen was the contrasting expression of chemokines and cell adhesion molecules. Lymphocyte chemokines, including the homeostatic chemokines CXCL13, CCL19 and CCL21, were significantly down-regulated in the spleen but up-regulated in the liver. Eosinophil (CCL11, CCL24), neutrophil (CXCL1) and monocyte (CXCL14, CCL12) chemokines and the cell adhesion molecules VCAM1, NCAM1, PECAM1 were up-regulated in the liver but unchanged in the spleen. Chemokines up-regulated in both organs were expressed at significantly higher levels in the liver. Co-ordinated expression of these genes probably contributes to the development of a chemotactic signalling gradient that promotes recruitment of effector cells to the liver, thereby facilitating the development of hepatic granulomas and fibrosis. Together these data provide, for the first time, a comprehensive overview of the molecular events occurring in the spleen during schistosomiasis and will substantially further our understanding of the local and systemic mechanisms driving the immunopathogenesis of this disease. Public Library of Science 2010-05-18 /pmc/articles/PMC2872641/ /pubmed/20502518 http://dx.doi.org/10.1371/journal.pntd.0000686 Text en Burke et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Burke, Melissa L. McManus, Donald P. Ramm, Grant A. Duke, Mary Li, Yuesheng Jones, Malcolm K. Gobert, Geoffrey N. Co-ordinated Gene Expression in the Liver and Spleen during Schistosoma japonicum Infection Regulates Cell Migration |
title | Co-ordinated Gene Expression in the Liver and Spleen during Schistosoma japonicum Infection Regulates Cell Migration |
title_full | Co-ordinated Gene Expression in the Liver and Spleen during Schistosoma japonicum Infection Regulates Cell Migration |
title_fullStr | Co-ordinated Gene Expression in the Liver and Spleen during Schistosoma japonicum Infection Regulates Cell Migration |
title_full_unstemmed | Co-ordinated Gene Expression in the Liver and Spleen during Schistosoma japonicum Infection Regulates Cell Migration |
title_short | Co-ordinated Gene Expression in the Liver and Spleen during Schistosoma japonicum Infection Regulates Cell Migration |
title_sort | co-ordinated gene expression in the liver and spleen during schistosoma japonicum infection regulates cell migration |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872641/ https://www.ncbi.nlm.nih.gov/pubmed/20502518 http://dx.doi.org/10.1371/journal.pntd.0000686 |
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