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Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor
R A Ezekowitz1, D J Williams, H Koziel
1Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts.
Abstract:
Human exposure to Pneumocystis carinii is common but, in the absence of acquired or genetic dysfunction of either cellular or humoral immunity, exposure rarely leads to illness. Although alveolar macrophages can degrade P. carinii, macrophage receptors involved in P. carinii recognition have not been clearly defined. Characterization of a predominant surface glycoprotein of the high mannose type led us to investigate the role of the macrophage mannose receptor in this process. We report here that binding and uptake of cultured rat P. carinii by human and rat alveolar macrophages is reduced by 90% in the presence of competitive inhibitors of mannose receptor activity and by adherence of alveolar macrophages to mannan-coated surfaces. Further, only those COS cells transfected with the human macrophage mannose receptor complementary DNA that express surface mannose receptors bind and ingest P. carinii. These studies establish that the macrophage mannose receptor is sufficient for uptake of P. carinii and emphasize the role of the alveolar macrophage in first-line host defence against P. carinii.
Insights
The mannose receptor on alveolar macrophages is crucial for recognizing and clearing Pneumocystis carinii. This finding highlights the macrophage mannose receptor
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Human exposure to Pneumocystis carinii is widespread, typically asymptomatic due to intact cellular and humoral immunity.
- Alveolar macrophages are involved in degrading P. carinii, but the specific receptors responsible for recognition were undefined.
- A high mannose-type surface glycoprotein on P. carinii prompted investigation into the mannose receptor's role.
Purpose of the Study:
- To investigate the role of the macrophage mannose receptor in the recognition and uptake of Pneumocystis carinii.
- To determine if the mannose receptor is sufficient for P. carinii uptake by macrophages.
Main Methods:
- Assessing P. carinii binding and uptake by human and rat alveolar macrophages using mannose receptor inhibitors and mannan-coated surfaces.
- Utilizing COS cells transfected with human macrophage mannose receptor complementary DNA to evaluate receptor-mediated phagocytosis.
- Characterizing a predominant high mannose-type surface glycoprotein on P. carinii.
Main Results:
- Mannose receptor activity inhibitors reduced P. carinii binding and uptake by 90%.
- Adherence to mannan-coated surfaces also decreased P. carinii uptake.
- COS cells expressing the human mannose receptor demonstrated binding and ingestion of P. carinii.
Conclusions:
- The macrophage mannose receptor is sufficient for Pneumocystis carinii uptake.
- This receptor plays a significant role in the alveolar macrophage's first-line host defense against P. carinii.
- Understanding this mechanism is vital for host defense strategies against P. carinii infections.