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Series GSE11005 Query DataSets for GSE11005
Status Public on Dec 22, 2008
Title Immune Responses to Pneumocystis Infection are Robust in Immunocompetent Mice but Absent in CD40 Ligand Deficient Mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary Pneumocystis is a pathogen of immunocompromised hosts but can also infect healthy hosts, in whom infection is rapidly controlled and cleared. To better understand the immune mechanisms contributing to clearance of infection, microarray methods were used to examine differential gene expression in the lungs of C57BL/6 and CD40 ligand knock-out (CD40L-KO) mice over time following exposure to Pneumocystis. Immuncompetent C57BL/6 mice, which control and clear infection efficiently, showed a robust response to infection characterized by the upregulation of 349 primarily immune-response associated genes. Temporal changes in the expression of these genes suggested that there was an early (week 2) primarily innate response, that waned without controlling infection; this were followed by primarily adaptive immune responses that peaked at week 5 and successfully cleared the infection. In conjunction with the latter, there was an increased expression of B cell associated (immunoglobulin) genes at week 6 that persisted through 11 weeks. In contrast, CD40L-KO mice, which are highly susceptible to developing severe Pneumocystis pneumonia, showed essentially no upregulation of immune-response associated genes at days 35 to 75. Immunohistochemical staining supported these observations by demonstrating an increase in CD4+, CD68+, and CD19+ cells in C57BL/6 but not CD40L-KO mice. Thus, the healthy host demonstrates a robust biphasic response to infection by Pneumocystis; CD40 ligand is an essential upstream regulator of the adaptive immune responses that efficiently control infection and prevent development of progressive pneumonia.
Keywords: Time course response Pneumocystis murina infection wild type versus CD40L-KO mice
 
Overall design In experiment 1, C57BL/6 and CD40L-KO mice were co-housed in 2 cages; one cage was exposed to a P. murina-infected seeder, while the second was unexposed. Mice (3 per group) were sacrificed at day 32. Because the initial study demonstrated very little change in gene expression in CD40L-KO mice, only C57BL/6 mice were used for experiments 2 and 3. In Experiment 2, three cages (10 animals/cage) were set up: 2 cages were exposed to P. murina, and one was unexposed. Animals (5 per cage) were sacrificed at days 34 and 41. In Experiment 3, which focused on gene expression early after exposure to P. murina, five cages (9-10 animals/cage) were set up, of which 3 were exposed and 2 were unexposed. Animals (1-3 per cage) were sacrificed at days 7, 14 and 21 of exposure. Experiment 4 was designed to verify the initial results in CD40L-KO mice, and included 5 unexposed controls and 4 mice exposed for 35 days.
 
Contributor(s) Hernandez-Novoa B, Bishop L, Logun C, Munson PJ, Elnekave E, Rangel Z, Barb J, Danner RL, Kovacs JA
Citation(s) 18467653
Submission date Mar 31, 2008
Last update date Feb 18, 2018
Contact name Joseph A. Kovacs
E-mail(s) jkovacs@mail.nih.gov
Organization name NIH
Department CCMD
Street address Bldg. 10, Room 2C145, MSC1662
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL81 [MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array
Samples (95)
GSM278232 Lung_CD40L-KO_32 days exposed to P. murina_rep1
GSM278233 Lung_CD40L-KO_32 days exposed to P. murina_rep2
GSM278234 Lung_CD40L-KO_32 days exposed to P. murina_rep3
Relations
BioProject PRJNA107087

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Supplementary file Size Download File type/resource
GSE11005_RAW.tar 212.5 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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