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Production of dengue virus-induced macrophage cytotoxin in vivo
Abstract:
We have observed that dengue virus-induced cytotoxic factor (CF) induces peritoneal and splenic macrophages in vitro to produce a cytotoxin (CF2). This study demonstrates also production of CF2 in vivo in DV-infected mice and following inoculation with CF. The cell-type responsible for CF2 production in vivo is the macrophage (M phi) as M phi-depleted mice failed to produce CF2. CF2 activity could not be observed in the serum or peritoneal fluid though it is produced in peritoneal M phi. Once stimulated, CF2 is present for 4 h in M phi. M phi can be restimulated to produce CF2 only after a refractory period of 48 h.
Insights
Dengue virus (DV) infection causes macrophages to produce a cytotoxin (CF2). This cytotoxin is produced in vivo by macrophages, but is not found in serum or peritoneal fluid.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Dengue virus (DV) infection is a significant global health concern.
- Cytotoxic factors (CF) are implicated in viral pathogenesis.
- Macrophages are key immune cells involved in antiviral responses.
Purpose of the Study:
- To investigate the production of a dengue virus-induced cytotoxic factor (CF2) in vivo.
- To identify the specific cell type responsible for CF2 production.
- To characterize the kinetics and localization of CF2 activity.
Main Methods:
- In vitro induction of macrophages to produce CF2 using dengue virus-induced cytotoxic factor (CF).
- Induction of CF2 production in vivo in dengue virus-infected mice and mice inoculated with CF.
- Macrophage depletion experiments to determine the cell type responsible for CF2 production.
- Analysis of serum, peritoneal fluid, and peritoneal macrophages for CF2 activity.
Main Results:
- Dengue virus-induced cytotoxic factor (CF) induces macrophages to produce a cytotoxin (CF2) in vitro.
- CF2 is produced in vivo in dengue virus-infected mice and following CF inoculation.
- Macrophages are the primary cell type responsible for in vivo CF2 production, as evidenced by studies with macrophage-depleted mice.
- CF2 activity is localized within peritoneal macrophages and not detected in serum or peritoneal fluid.
- Once stimulated, CF2 is present within macrophages for 4 hours.
- Macrophages require a 48-hour refractory period before they can be restimulated to produce CF2.
Conclusions:
- Macrophages play a critical role in producing cytotoxic factors during dengue virus infection.
- The cytotoxic factor CF2 is macrophage-derived and acts locally within these cells.
- Understanding the dynamics of CF2 production and its refractory period may offer insights into dengue pathogenesis and potential therapeutic targets.