Total lung gene expression data of Pneumocystis-infected wildtype and IFN-gamma knockout mice.

ABSTRACT: Pulmonary hypertension (PH) is a disease of diverse etiology. While primary PH can develop in the absence of prior disease, PH more commonly develops in conjunction with other pulmonary pathologies. We previously reported a mouse model in which PH occurs as a sequelae of Pneumocystis infection in the context of transient CD4 depletion. Here, we demonstrate that instead of the expected Th2 pathways, the Th1 cytokine IFN-M-NM-3 was essential for the development of PH, as wild type mice developed PH, but not IFN-M-NM-3 knockout mice. Because gene expression analysis showed few strain differences that were not immune function related, we focused on those responses as potential pathologic mechanisms. While there were several differences in cellular and cytokine response that warrant further examination, we focused on three important aspects. First, if CD4 cells were continuously depleted, but the infection was limited by antibiotic treatment, then PH did not occur, confirming that CD4 T-cells are required for PH development. Second, although CD8 T-cells are implicated in the pathology of unabated Pneumocystis pneumonia, they did not have a role in the onset of PH. Finally, although there are differences in the amounts of the pulmonary immune cells, differences existed in phenotypes of immune cells that correlated with PH, such as elevated CD204 expression in lung CD11c+ cells. Two groups of BALB/c mice (3 per group) were infected i.t. with 10e7 Pneumocystis; one of those groups also received 4 injections of CD4 T-cell depleting antibodies beginning 3 days prior to infection and ending 7 days after infection. A third group was IFN-gamma knockout mice infected with Pneumocystis and depleted of CD4 cells in the same way. A fourth group of control non-treated BALB/c mice were also used. AT 38 days post infection, lung tissues were taken, and RNA was extracted to allow for differential gene expression analysis

ORGANISM(S): Mus musculus

SUBMITTER: Steve Swain 

PROVIDER: E-GEOD-51750 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress