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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...

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Autores principales: Cheng, Bi-Hua, Liu, Yunlong, Xuei, Xiaoling, Liao, Chung-Ping, Lu, Debao, Lasbury, Mark E, Durant, Pamela J, Lee, Chao-Hung
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
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.
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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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