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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL055002-10
Application #
6184324
Study Section
Special Emphasis Panel (ZRG1-AARR-3 (04))
Project Start
1990-07-01
Project End
2004-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
10
Fiscal Year
2000
Total Cost
$392,451
Indirect Cost
Name
Trudeau Institute, Inc.
Department
Type
DUNS #
City
Saranac Lake
State
NY
Country
United States
Zip Code
12983
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
Swain, Steve D; Meissner, Nicole; Han, Soo et al. (2011) Pneumocystis infection in an immunocompetent host can promote collateral sensitization to respiratory antigens. Infect Immun 79:1905-14
Wiley, James A; Harmsen, Allen G (2008) Pneumocystis infection enhances antibody-mediated resistance to a subsequent influenza infection. J Immunol 180:5613-24
Swain, Steve D; Han, Soo; Harmsen, Ann et al. (2007) Pulmonary hypertension can be a sequela of prior Pneumocystis pneumonia. Am J Pathol 171:790-9
Meissner, Nicole; Rutkowski, Melanie; Harmsen, Ann L et al. (2007) Type I interferon signaling and B cells maintain hemopoiesis during Pneumocystis infection of the lung. J Immunol 178:6604-15
Swain, Steve D; Meissner, Nicole N; Harmsen, Allen G (2006) CD8 T cells modulate CD4 T-cell and eosinophil-mediated pulmonary pathology in pneumocystis pneumonia in B-cell-deficient mice. Am J Pathol 168:466-75
Meissner, Nicole N; Swain, Steve; Tighe, Mike et al. (2005) Role of type I IFNs in pulmonary complications of Pneumocystis murina infection. J Immunol 174:5462-71
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
Swain, Steve D; Wright, Terry W; Degel, Peter M et al. (2004) Neither neutrophils nor reactive oxygen species contribute to tissue damage during Pneumocystis pneumonia in mice. Infect Immun 72:5722-32
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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