Pneumocystis carinii is a major pathogen of patients with human immunodeficiency virus infection. The immune responses to P. carinii are poorly under-stood, but cytokines may play a role in both clearing P. carinii infection and in the hypoxia associated with P. carinii pneumonia that may be exacerbated following initiation of therapy. We have completed a study with Dr. Vogel examining the effects of interleukin-12 (IL-12) in SCID mice with P. carinii pneumonia. In this model no effect on P. carinii pneumonia was seen when IL-12 was administered either at the time of exposure to P. carinii or 4 weeks after exposure. We have begun studies to examine the role of the major surface glycoprotein in inducing protective immune responses in mice. In the future, we plan to use the SCID mouse model as well as other immunodeficient mice to evaluate further the role of indivi-dual cytokines and other immunoregulatory molecules in modulating P. carinii infection. It is hoped that these studies will provide insights into the role of cytokines in P. carinii pneumonia 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 #
1Z01CL000146-06
Application #
6289396
Study Section
Special Emphasis Panel (CCMB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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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