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Genetic control of resistance to murine malaria
Abstract:
Strain variation in the level of resistance to malaria was investigated in inbred mice after infection with Plasmodium chabaudi. Following intraperitoneal infection with the typing dose of parasitized erythrocytes, mice of 11 inbred strains could be separated using survival time as the criterium into resistant and susceptible groups. Genetic analysis of F1 hybrid and backcross progeny derived from one of the most resistant (B10.A) and from the most susceptible (A/J) strains as parents suggested that host resistance in this strain combination was genetically controlled by a dominant, non-H-2-linked, autosomal gene or closely linked genes. Analysis of the mechanisms of resistance to P chabaudi showed (1) phenotypic expression of the resistance gene was apparent within 6 days of infection as a significant difference between resistant and susceptible mice in the level of parasitemia; (2) the level of host NK cell activity was not related to the level of host resistance to malaria; (3) compared with susceptible A/J mice, resistant B10.A hosts had an augmented erythropoietic response during the course of malaria as well as during phenylhydrazine-induced anemia and (4) treatment with BCG or P acnes resulted in an equal degree of protection, measured by parasitemia and survival, in both resistant and susceptible mice.
Insights
Malaria resistance in mice infected with Plasmodium chabaudi is controlled by a single dominant gene. This genetic control influences parasitemia levels and erythropoiesis, but not NK cell activity.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Malaria remains a significant global health challenge.
- Understanding host genetic factors influencing malaria resistance is crucial for developing effective control strategies.
Purpose of the Study:
- To investigate strain variation in malaria resistance in inbred mice infected with Plasmodium chabaudi.
- To identify the genetic basis and underlying mechanisms of host resistance.
Main Methods:
- Infection of 11 inbred mouse strains with Plasmodium chabaudi.
- Genetic analysis of F1 hybrid and backcross progeny.
- Assessment of parasitemia, survival, NK cell activity, erythropoiesis, and response to BCG/P. acnes treatment.
Main Results:
- Mouse strains segregated into resistant and susceptible groups based on survival time.
- A dominant, non-H-2-linked, autosomal gene controls resistance in the B10.A x A/J strain combination.
- Resistance is associated with lower parasitemia and augmented erythropoiesis, independent of NK cell activity.
Conclusions:
- Host resistance to Plasmodium chabaudi is genetically determined by a specific autosomal gene.
- The identified gene influences key physiological responses during infection, offering insights into malaria pathogenesis.