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Opsonization-enhanced phagocytosis of foot-and-mouth disease virus
K C McCullough1, D Parkinson, J R Crowther
1Department of Immunology, Animal Virus Research Institute, Woking, Surrey.
Abstract:
Using isolated peritoneal adherent cells, in which monocytes and macrophages dominate, the uptake and destruction of foot-and-mouth disease virus (FMDV) was enhanced by the opsonization with mAb of particular epitope specificity. This was seen under conditions in which virus infectivity was not neutralized, as determined by in vitro assay. Activation of macrophages in vivo further enhanced the uptake of opsonized virus, presumably by increasing the percentage of phagocytosing cells. The enhanced phagocytosis required opsonization and apparently made use of FcR+ cells, because pepsin-treated antibodies and separated F(ab')2 fragments did not enhance the capacity of the peritoneal cells to react with the virus. The reaction also relied on active phagocytosis, because inhibition of phagocytosis using silica interfered with the binding of both virus alone and virus/antibody complexes. This evidence shows that the previous in vivo observations (McCullough et al., 1986b) of enhanced protection by the mAb can be related to active phagocytosis of virus and virus/antibody complexes. The reaction is not passive adsorption to the monocyte surface, but an active phagocytosis of the virus or the complex.
Insights
Monoclonal antibodies (mAbs) targeting specific foot-and-mouth disease virus (FMDV) epitopes enhance macrophage uptake and destruction of the virus. This process involves active phagocytosis, not passive adsorption, leading to improved protection.
Area of Science:
- Immunology
- Virology
Background:
- Monocytes and macrophages play a crucial role in viral clearance.
- Foot-and-mouth disease virus (FMDV) poses a significant threat to livestock.
- Antibody-mediated enhancement of phagocytosis is a key immune mechanism.
Purpose of the Study:
- To investigate the mechanism by which monoclonal antibodies (mAbs) enhance the uptake and destruction of FMDV by peritoneal cells.
- To determine if enhanced phagocytosis is dependent on antibody opsonization and Fc receptor engagement.
Main Methods:
- Isolated peritoneal adherent cells, enriched for monocytes and macrophages, were used.
- Opsonization of FMDV with specific mAbs was performed.
- In vitro assays were used to measure virus uptake and infectivity.
- Inhibition of phagocytosis using silica was employed.
- Pepsin-treated antibodies and F(ab')2 fragments were used to assess the role of Fc receptors.
Main Results:
- Opsonization of FMDV with specific mAbs significantly enhanced uptake and destruction by peritoneal cells, even without viral neutralization.
- In vivo activation of macrophages further increased the uptake of opsonized virus.
- Enhanced phagocytosis required antibody opsonization and engagement of Fc receptors (FcR+ cells).
- Inhibition of phagocytosis disrupted the binding of both FMDV and antibody-FMDV complexes.
- The reaction was identified as active phagocytosis, not passive adsorption.
Conclusions:
- Monoclonal antibody opsonization of FMDV triggers active phagocytosis by FcR+ cells, primarily monocytes and macrophages.
- This enhanced phagocytosis mechanism contributes to the in vivo protection observed previously.
- The findings elucidate a critical pathway for antibody-mediated antiviral defense involving active cellular uptake.