RGD Reference Report - Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages. - Rat Genome Database

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Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages.

Authors: Cheng, BH  Liu, Y  Xuei, X  Liao, CP  Lu, D  Lasbury, ME  Durant, PJ  Lee, CH 
Citation: Cheng BH, etal., BMC Microbiol. 2010 Apr 8;10:103.
RGD ID: 4144112
Pubmed: PMID:20377877   (View Abstract at PubMed)
PMCID: PMC2858032   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2180-10-103   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Pneumocystis Infections  ISORT1-Db1 (Rattus norvegicus)4144112; 4144112mRNA:increased expression:bronchoalveolar lavage and alveolar macrophage (rat)RGD 
Pneumocystis Infections  IEP 4144112mRNA:increased expression:bronchoalveolar lavage and alveolar macrophage (rat)RGD 
pneumocystosis  ISORT1-Bb (Rattus norvegicus)4144112; 4144112 RGD 
pneumocystosis  ISONos2 (Rattus norvegicus)4144112; 4144112mRNA:increased expression:alveolar macrophageRGD 
pneumocystosis  IEP 4144112mRNA:increased expression:alveolar macrophageRGD 
pneumocystosis  IEP 4144112 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to dexamethasone stimulus  IEP 4144112 RGD 
defense response to fungus  IEP 4144112Pneumocystis cariniiRGD 
response to dexamethasone  IEP 4144112 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos2  (nitric oxide synthase 2)
RT1-Bb  (RT1 class II, locus Bb)
RT1-Db1  (RT1 class II, locus Db1)

Genes (Mus musculus)
H2-Ab1  (histocompatibility 2, class II antigen A, beta 1)
H2-Eb1  (histocompatibility 2, class II antigen E beta)
Nos2  (nitric oxide synthase 2, inducible)

Genes (Homo sapiens)
HLA-DQB1  (major histocompatibility complex, class II, DQ beta 1)
HLA-DRB1  (major histocompatibility complex, class II, DR beta 1)
NOS2  (nitric oxide synthase 2)


Additional Information