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Evidence for immune-mediated destruction as mechanism for LCMV-induced anemia in persistently infected mice
1Department of Biology, Rensselaer Polytechnic Institute, Troy, New York.
Abstract:
A docile substrain of lymphocytic choriomeningitis virus (LCMV) causes a persistent infection in adult C3HeB mice and induces a severe anemia, which, unlike the viremia, eventually resolves. Measurements of red blood cell (RBC) survival rates demonstrated an increased rate of RBC clearance in these animals, indicating a hemolytic process for the anemia. Normal clearance rates of RBCs from infected mice transfused into control mice suggested that there was not an intrinsic defect in these cells. It also appeared that RBC destruction was immune-mediated, as cyclophosphamide treatments prevented the onset of anemia in infected mice, whereas adoptive transfer (AT) of immune splenocytes into immunocompromised mice reestablished the condition. The AT experiments also demonstrated that the onset of anemia correlated with the functional state of the immune cells. In addition, opsonization of RBCs was demonstrated by macrophage phagocytosis, and the appearance of opsonized RBCs corresponded with the course of the anemia. These findings support a hypothesis of RBC opsonization and subsequent phagocytosis by macrophages of the reticuloendothelial system as the mechanism for RBC destruction in LCMV-induced hemolytic anemia.
Insights
A persistent lymphocytic choriomeningitis virus (LCMV) infection in mice causes hemolytic anemia. Red blood cell destruction is immune-mediated, involving macrophage phagocytosis of opsonized red blood cells.
Area of Science:
- Immunology
- Virology
- Hematology
Background:
- Lymphocytic choriomoriomeningitis virus (LCMV) infection can lead to persistent infections and anemia in mice.
- The anemia associated with LCMV infection is severe but eventually resolves, unlike the viremia.
Purpose of the Study:
- To investigate the mechanism of red blood cell (RBC) destruction in LCMV-induced hemolytic anemia.
- To determine if the anemia is due to an intrinsic RBC defect or an immune-mediated process.
Main Methods:
- Measuring RBC survival rates in infected and control mice.
- Performing transfusion experiments with RBCs from infected mice into control mice.
- Utilizing cyclophosphamide treatment and adoptive transfer (AT) of immune splenocytes to assess immune mediation.
- Observing macrophage phagocytosis of opsonized RBCs.
Main Results:
- Increased RBC clearance rates in LCMV-infected mice indicated a hemolytic process.
- Normal RBC clearance in transfused control mice ruled out intrinsic RBC defects.
- Cyclophosphamide prevented anemia, while AT of immune splenocytes reestablished it, confirming immune mediation.
- Opsonization of RBCs and subsequent macrophage phagocytosis correlated with the anemia's course.
Conclusions:
- LCMV-induced anemia in mice is a hemolytic process.
- RBC destruction is immune-mediated, involving opsonization and phagocytosis by macrophages.
- The functional state of immune cells is critical for the onset of anemia.