Results of recent studies in this laboratory indicate that immunocompetent mice become colonized with P. carinii when they are co- housed with other infected mice. The P. carinii persist in these mice for 6-7 weeks before an acquired immune response develops and clears the organism. We thus hypothesize that P. carinii can colonize immunocompetent hosts by escaping non-specific immune system recognition. This allows the organism to be passed from host to host. Furthermore, we hypothesize that this infection causes little pathology because it is cleared by acquired immune responses before it can increase in numbers to the point where it can cause damage to the host. To test this hypothesis, experiments to accomplish the following specific aims will be performed. 1. To determine how host-parasite interactions between P. carinii and an immunocompetent host exposed to P. carinii by co-housing affects the epidemiology and pathogenesis of PCP. 2. To determine what must occur in an immunocompetent host to initiate an acquired immune response to P. carinii. 3. To determine the role of cell-mediated immunity in resistance to primary infection and secondary challenge of the immunocompetent host with P. carinii. 4. To determine the role of B cell-dependent immunity to resistance to primary infection and secondary challenge of the immunocompetent host with P. carinii. It is expected that results of these proposed studies will better our understanding of how the interaction of P. carinii and the immune system of the immunocompetent host affects the epidemiology, transmission and pathogenesis of P. carinii infection. We believe it is important to understand these interactions first in the immunocompetent host so that we can in turn better understand the basis of susceptibility of AIDS patients to P. carinii.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Special Emphasis Panel (ZRG1-AARR-3 (04))
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Trudeau Institute, Inc.
Saranac Lake
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Swain, Steve D; Meissner, Nicole N; Siemsen, Dan W et al. (2012) Pneumocystis elicits a STAT6-dependent, strain-specific innate immune response and airway hyperresponsiveness. Am J Respir Cell Mol Biol 46:290-8
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Meissner, Nicole N; Lund, Frances E; Han, Soo et al. (2005) CD8 T cell-mediated lung damage in response to the extracellular pathogen pneumocystis is dependent on MHC class I expression by radiation-resistant lung cells. J Immunol 175:8271-9
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Swain, Steve D; Lee, Sena J; Nussenzweig, Michel C et al. (2003) Absence of the macrophage mannose receptor in mice does not increase susceptibility to Pneumocystis carinii infection in vivo. Infect Immun 71:6213-21

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