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Inhibition of murine macrophage protein kinase C activity by nonviable Histoplasma capsulatum
J E Wolf1, S E Massof, J R Sherwin
1Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Abstract:
Ingestion of Histoplasma capsulatum yeast cells inhibits the oxidative burst response of murine macrophages (M phi's). Since protein kinase C (PKC) is believed to be an integral part of the signal transduction pathway involved in the production of reactive oxygen intermediates, we investigated the relationship between PKC activity and oxidative burst inhibition in H. capsulatum-containing murine peritoneal M phi's. An inhibitory effect on both basal and phorbol myristate acetate-mobilized membrane PKC activities was observed in M phi's which had ingested H. capsulatum but not latex spheres. These results suggest that one way in which H. capsulatum may disrupt the oxidative burst is through a PCK-dependent mechanism.
Insights
Histoplasma capsulatum yeast cells disrupt macrophage oxidative burst response. This disruption involves protein kinase C (PKC) signaling, suggesting a PKC-dependent mechanism for immune evasion by the fungus.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Macrophages are key immune cells that use oxidative burst to eliminate pathogens.
- Histoplasma capsulatum is a fungus that can infect macrophages.
- Protein kinase C (PKC) is involved in signaling pathways that regulate cellular responses, including oxidative burst.
Purpose of the Study:
- To investigate the role of protein kinase C (PKC) in the inhibition of the macrophage oxidative burst by Histoplasma capsulatum.
- To determine if H. capsulatum interferes with PKC activity in macrophages.
Main Methods:
- Murine peritoneal macrophages were infected with Histoplasma capsulatum yeast cells or latex spheres.
- Protein kinase C (PKC) activity in macrophage membranes was measured.
- Basal and phorbol myristate acetate (PMA)-stimulated PKC activity was assessed.
Main Results:
- Ingestion of H. capsulatum, but not latex spheres, inhibited the oxidative burst response of macrophages.
- H. capsulatum ingestion led to the inhibition of both basal and PMA-mobilized membrane PKC activities.
- Latex sphere ingestion did not affect PKC activity.
Conclusions:
- Histoplasma capsulatum inhibits the macrophage oxidative burst.
- This inhibition appears to be mediated by a protein kinase C (PKC)-dependent mechanism.
- H. capsulatum may evade the host immune response by disrupting macrophage signaling pathways involving PKC.