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Phagocytosis of herpes simplex virus by human granulocytes and monocytes
J A Van Strijp1, K P Van Kessel, M E van der Tol
1Laboratory for Microbiology, University of Utrecht, The Netherlands.
Abstract:
Polymorphonuclear leukocytes (PMN) can mediate cytotoxic reactions against virus infected targets cells. We observed very efficient binding of PMN to HSV-infected fibroblasts when loaded with HSV-specific antibodies. Using electron microscopy, infected fibroblasts were found to be totally surrounded by PMN and the phagocytosis of virions and fragments of infected cells was demonstrated. To quantify and study this phenomenon, and to compare PMN with monocytes, we developed radiometric and fluorometric phagocytosis assays. Leukocytes were mixed with [3H]glucosamine- or FITC-labeled virus and incubated at 37 degrees C. PMN associated radioactivity or fluorescence per cell as measured by flow cytometry was determined. PMN phagocytosis was dependent on the presence of specific anti-HSV antibodies and could be enhanced by addition of complement. Monocytes were also able to phagocytize virions; however, the rate of uptake was less than that for PMN. Under optimal conditions the total amount of herpes simplex particles that could be associated with one PMN or monocyte was about 10,000. PMN and monocytes are capable of phagocytosis of HSV. This may be an important factor in preventing the spread of infection in vivo.
Insights
Polymorphonuclear leukocytes (PMN) efficiently bind to and phagocytize herpes simplex virus (HSV)-infected cells, especially with antibody support. This phagocytosis by PMN and monocytes may be crucial for controlling HSV infection in the body.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMN) play a role in cellular immune responses.
- Herpes Simplex Virus (HSV) establishes persistent infections, necessitating understanding of immune clearance mechanisms.
Purpose of the Study:
- To investigate the phagocytic capabilities of PMN and monocytes against HSV-infected cells.
- To quantify and compare the phagocytosis efficiency of PMN and monocytes for HSV.
Main Methods:
- Developed radiometric and fluorometric phagocytosis assays using labeled HSV.
- Utilized electron microscopy to visualize PMN-target cell interactions.
- Quantified phagocytosis via flow cytometry measuring associated radioactivity or fluorescence.
Main Results:
- PMN demonstrated highly efficient binding and phagocytosis of HSV-infected fibroblasts, enhanced by specific antibodies and complement.
- Electron microscopy confirmed PMN surrounding infected cells and ingesting virions and cellular debris.
- Monocytes also phagocytized HSV, but at a lower rate compared to PMN.
- Both cell types could associate with approximately 10,000 herpes simplex particles under optimal conditions.
Conclusions:
- PMN and monocytes are capable of phagocytizing HSV, representing a significant cellular defense mechanism.
- Antibody-dependent phagocytosis by PMN is a key factor in combating HSV infection.
- These findings highlight the importance of PMN and monocytes in controlling HSV spread in vivo.