Abstract
BackgroundThe major surface glycoprotein (Msg) of Pneumocystis is encoded by approximately 50 to 80 unique but related genes. Msg diversity may represent a mechanism for immune escape from host T cell responses. We examined splenic T cell proliferative and cytokine as well as serum antibody responses to recombinant and native Pneumocystis antigens in immunized or Pneumocystis-infected mice. In addition, immune responses were examined in 5 healthy humans.ResultsProliferative responses to each of two recombinant Msg variant proteins were seen in mice immunized with either recombinant protein, but no proliferation to these antigens was seen in mice immunized with crude Pneumocystis antigens or in mice that had cleared infection, although the latter animals demonstrated proliferative responses to crude Pneumocystis antigens and native Msg. IL-17 and MCP-3 were produced in previously infected animals in response to the same antigens, but not to recombinant antigens. Antibody responses to the recombinant P. murina Msg variant proteins were seen in all groups of animals, demonstrating that all groups were exposed to and mounted immune responses to Msg. No human PBMC samples proliferated following stimulation with P. jirovecii Msg, while antibody responses were detected in sera from 4 of 5 samples.ConclusionsCross-reactive antibody responses to Msg variants are common, while cross-reactive T cell responses are uncommon; these results support the hypothesis that Pneumocystis utilizes switching of Msg variant expression to avoid host T cell responses.
Highlights
The major surface glycoprotein (Msg) of Pneumocystis is encoded by approximately 50 to 80 unique but related genes
This eliminated cross-reactive immune responses to the vector-encoded portion of the recombinant protein which we identified in preliminary studies
This study has demonstrated that while cross-reactive proliferative responses to two distinct recombinant Msg variants were induced by multiple immunizations with recombinant Msg protein, proliferative responses to these recombinant proteins were not seen following immunization with crude Pneumocystis antigens, which contain Msg, or following natural infection in a healthy host
Summary
The major surface glycoprotein (Msg) of Pneumocystis is encoded by approximately 50 to 80 unique but related genes. Msg diversity may represent a mechanism for immune escape from host T cell responses. We examined splenic T cell proliferative and cytokine as well as serum antibody responses to recombinant and native Pneumocystis antigens in immunized or Pneumocystis-infected mice. Pneumocystis is a fungus that can cause severe pneumonia in immunosuppressed hosts, especially those with HIV infection, but that can cause pulmonary infection that is cleared by a robust immune response in healthy hosts. The multiple Msg variants strongly suggests that Pneumocystis has developed a mechanism for antigenic variation, similar to other organisms such as trypanosomes or Borrelia [8,14]. Pneumocystis is a pathogen of immunosuppressed hosts, Pneumocystis can infect and induce a brisk and effective immune response in immunocompetent hosts [15,16]. Antigenic variation presumably evolved to evade host responses in the latter, given that immunosuppressed hosts would likely rarely be encountered in nature
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