of Work: Pneumocystis carinii is a major pathogen of patients with HIV infection. The immune responses to P. carinii are poorly understood, but cytokines may clay a role both in clearing P. carinii infection and in the hypoxia associated with P. carinii pneumonia (PCP) that may be exacerbated following initiation of therapy. Collaborative studies with investigators at Indiana University continue. Based on preliminary polymerase chain reaction studies, investigators at Indiana University are currently examining the potential role of IL-10 in the pathogenesis of PCP using a CD4 depleted mouse model. In addition, we have completed a study with Dr. Vogel examining the effects of IL-12 in scid mice with PCP. In this model no effect on PCP was seen when IL-12 was administered either at the time of exposure to P. carinii or 4 weeks after exposure. In the future, we plan to use the scid mouse model to further evaluate the role of individual cytokines in modulating P. carinii infection. It is hoped that these studies will provide insights into the role of cytokines in PCP, and may provide mechanisms for increasing clearance or decreasing the inflammation that may be causing hypoxia.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL000146-04
Application #
6161424
Study Section
Special Emphasis Panel (CCMD)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Kutty, Geetha; Maldarelli, Frank; Achaz, Guillaume et al. (2008) Variation in the major surface glycoprotein genes in Pneumocystis jirovecii. J Infect Dis 198:741-9
Hernandez-Novoa, Beatriz; Bishop, Lisa; Logun, Carolea et al. (2008) Immune responses to Pneumocystis murina are robust in healthy mice but largely absent in CD40 ligand-deficient mice. J Leukoc Biol 84:420-30
Burbelo, Peter D; Ching, Kathryn H; Mattson, Thomas L et al. (2007) Rapid antibody quantification and generation of whole proteome antibody response profiles using LIPS (luciferase immunoprecipitation systems). Biochem Biophys Res Commun 352:889-95
Vestereng, Vibeke H; Kovacs, Joseph A (2004) Inability of Pneumocystis organisms to incorporate bromodeoxyuridine suggests the absence of a salvage pathway for thymidine. Microbiology 150:1179-82
Vestereng, Vibeke H; Bishop, Lisa R; Hernandez, Beatriz et al. (2004) Quantitative real-time polymerase chain-reaction assay allows characterization of pneumocystis infection in immunocompetent mice. J Infect Dis 189:1540-4
Vestereng, V H; Kovacs, J A (2001) Recombinant CD40 ligand administration does not decrease intensity of Pneumocystis carinii infection in scid mice. J Eukaryot Microbiol Suppl:153S-154S