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Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages
BACKGROUND: Pneumocystis pneumonia is a common opportunistic disease in AIDS patients. The alveolar macrophage is an important effector cell in the clearance of Pneumocystis organisms by phagocytosis. However, both the number and phagocytic activity of alveolar macrophages are decreased in Pneumocys...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858032/ https://www.ncbi.nlm.nih.gov/pubmed/20377877 http://dx.doi.org/10.1186/1471-2180-10-103 |
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author | Cheng, Bi-Hua Liu, Yunlong Xuei, Xiaoling Liao, Chung-Ping Lu, Debao Lasbury, Mark E Durant, Pamela J Lee, Chao-Hung |
author_facet | Cheng, Bi-Hua Liu, Yunlong Xuei, Xiaoling Liao, Chung-Ping Lu, Debao Lasbury, Mark E Durant, Pamela J Lee, Chao-Hung |
author_sort | Cheng, Bi-Hua |
collection | PubMed |
description | BACKGROUND: Pneumocystis pneumonia is a common opportunistic disease in AIDS patients. The alveolar macrophage is an important effector cell in the clearance of Pneumocystis organisms by phagocytosis. However, both the number and phagocytic activity of alveolar macrophages are decreased in Pneumocystis infected hosts. To understand how Pneumocystis inactivates alveolar macrophages, Affymetrix GeneChip(® )RG-U34A DNA microarrays were used to study the difference in global gene expression in alveolar macrophages from uninfected and Pneumocystis carinii-infected Sprague-Dawley rats. RESULTS: Analyses of genes that were affected by Pneumocystis infection showed that many functions in the cells were affected. Antigen presentation, cell-mediated immune response, humoral immune response, and inflammatory response were most severely affected, followed by cellular movement, immune cell trafficking, immunological disease, cell-to-cell signaling and interaction, cell death, organ injury and abnormality, cell signaling, infectious disease, small molecular biochemistry, antimicrobial response, and free radical scavenging. Since rats must be immunosuppressed in order to develop Pneumocystis infection, alveolar macrophages from four rats of the same sex and age that were treated with dexamethasone for the entire eight weeks of the study period were also examined. With a filter of false-discovery rate less than 0.1 and fold change greater than 1.5, 200 genes were found to be up-regulated, and 144 genes were down-regulated by dexamethasone treatment. During Pneumocystis pneumonia, 115 genes were found to be up- and 137 were down-regulated with the same filtering criteria. The top ten genes up-regulated by Pneumocystis infection were Cxcl10, Spp1, S100A9, Rsad2, S100A8, Nos2, RT1-Bb, Lcn2, RT1-Db1, and Srgn with fold changes ranging between 12.33 and 5.34; and the top ten down-regulated ones were Lgals1, Psat1, Tbc1d23, Gsta1, Car5b, Xrcc5, Pdlim1, Alcam, Cidea, and Pkib with fold changes ranging between -4.24 and -2.25. CONCLUSIONS: In order to survive in the host, Pneumocystis organisms change the expression profile of alveolar macrophages. Results of this study revealed that Pneumocystis infection affects many cellular functions leading to reduced number and activity of alveolar macrophages during Pneumocystis pneumonia. |
format | Text |
id | pubmed-2858032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28580322010-04-22 Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages Cheng, Bi-Hua Liu, Yunlong Xuei, Xiaoling Liao, Chung-Ping Lu, Debao Lasbury, Mark E Durant, Pamela J Lee, Chao-Hung BMC Microbiol Research article BACKGROUND: Pneumocystis pneumonia is a common opportunistic disease in AIDS patients. The alveolar macrophage is an important effector cell in the clearance of Pneumocystis organisms by phagocytosis. However, both the number and phagocytic activity of alveolar macrophages are decreased in Pneumocystis infected hosts. To understand how Pneumocystis inactivates alveolar macrophages, Affymetrix GeneChip(® )RG-U34A DNA microarrays were used to study the difference in global gene expression in alveolar macrophages from uninfected and Pneumocystis carinii-infected Sprague-Dawley rats. RESULTS: Analyses of genes that were affected by Pneumocystis infection showed that many functions in the cells were affected. Antigen presentation, cell-mediated immune response, humoral immune response, and inflammatory response were most severely affected, followed by cellular movement, immune cell trafficking, immunological disease, cell-to-cell signaling and interaction, cell death, organ injury and abnormality, cell signaling, infectious disease, small molecular biochemistry, antimicrobial response, and free radical scavenging. Since rats must be immunosuppressed in order to develop Pneumocystis infection, alveolar macrophages from four rats of the same sex and age that were treated with dexamethasone for the entire eight weeks of the study period were also examined. With a filter of false-discovery rate less than 0.1 and fold change greater than 1.5, 200 genes were found to be up-regulated, and 144 genes were down-regulated by dexamethasone treatment. During Pneumocystis pneumonia, 115 genes were found to be up- and 137 were down-regulated with the same filtering criteria. The top ten genes up-regulated by Pneumocystis infection were Cxcl10, Spp1, S100A9, Rsad2, S100A8, Nos2, RT1-Bb, Lcn2, RT1-Db1, and Srgn with fold changes ranging between 12.33 and 5.34; and the top ten down-regulated ones were Lgals1, Psat1, Tbc1d23, Gsta1, Car5b, Xrcc5, Pdlim1, Alcam, Cidea, and Pkib with fold changes ranging between -4.24 and -2.25. CONCLUSIONS: In order to survive in the host, Pneumocystis organisms change the expression profile of alveolar macrophages. Results of this study revealed that Pneumocystis infection affects many cellular functions leading to reduced number and activity of alveolar macrophages during Pneumocystis pneumonia. BioMed Central 2010-04-08 /pmc/articles/PMC2858032/ /pubmed/20377877 http://dx.doi.org/10.1186/1471-2180-10-103 Text en Copyright ©2010 Cheng et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research article Cheng, Bi-Hua Liu, Yunlong Xuei, Xiaoling Liao, Chung-Ping Lu, Debao Lasbury, Mark E Durant, Pamela J Lee, Chao-Hung Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages |
title | Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages |
title_full | Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages |
title_fullStr | Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages |
title_full_unstemmed | Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages |
title_short | Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages |
title_sort | microarray studies on effects of pneumocystis carinii infection on global gene expression in alveolar macrophages |
topic | Research article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858032/ https://www.ncbi.nlm.nih.gov/pubmed/20377877 http://dx.doi.org/10.1186/1471-2180-10-103 |
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