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Genetic association of murine susceptibility to Brugia malayi microfilaraemia
Abstract:
The influence of host genetics on susceptibility of mice to Brugia malayi microfilariae and its possible mechanism were studied. There was a strain-association for duration and peak level of microfilaraemia: CBA/CaJ, C3H/HeJ, DBA/1J, AuSs/J and A.S.w/Sn had a short duration (3-5 days) and low parasitemia (19-26 parasites/100 microliters blood) compared to C57Br/cdJ, AKR/J, C57BL/6J, 129/J, BALB/cJ, DBA/2J, B10.D2/NSn, B10.D2/OSn and SJL/J (duration of 58-73 days, peak parasitaemia of 58-74 parasites/100 microliters blood). Relative resistance to microfilariae was not related to the H-2 complex as determined in studies of congenic C3H.B10 (H-2b) and B10.H-2k mice and their background strains. This trait was inherited in a dominant fashion and involved a single or small number of genes. Serum anti-microfilarial antibodies reached highest levels in strains with a long duration compared to those with a short duration of parasitaemia (geometric mean titres of 1:13450 vs 1:284). The distribution of 51Cr-labelled microfilariae among the livers, spleens, lungs and kidneys of a resistant (CBA/CaJ) and a susceptible (C57BL/6J) strain was similar. Transfer of immune lymphoid cells or sera between histocompatible (H-2k) resistant CBA/CaJ mice and susceptible C57Br/cdJ animals did not alter the duration of microfilaraemia.
Insights
Host genetics significantly impacts Brugia malayi microfilariae susceptibility in mice. Resistance is inherited dominantly, involving few genes, and is not linked to the H-2 complex.
Area of Science:
- Immunology
- Genetics
- Parasitology
Background:
- Host genetics plays a crucial role in determining susceptibility to parasitic infections.
- Understanding genetic factors influencing Brugia malayi infection is vital for developing control strategies.
Purpose of the Study:
- To investigate the influence of host genetics on mouse susceptibility to Brugia malayi microfilariae.
- To elucidate the underlying mechanisms of genetic resistance or susceptibility.
Main Methods:
- Infection of various inbred mouse strains with Brugia malayi microfilariae.
- Monitoring of microfilaremia duration and peak parasitemia.
- Analysis of H-2 complex association and inheritance patterns.
- Measurement of anti-microfilarial antibody levels.
- Assessment of microfilariae distribution in organs.
- Cell and serum transfer experiments.
Main Results:
- Significant strain-associated differences in microfilaremia duration and peak levels were observed.
- Resistant strains exhibited short microfilaremia (3-5 days, 19-26 parasites/100 µL), while susceptible strains showed prolonged infection (58-73 days, 58-74 parasites/100 µL).
- Resistance was not linked to the H-2 complex but was inherited in a dominant fashion, suggesting a single or few genes.
- Higher anti-microfilarial antibody titers were found in susceptible strains with longer parasitemia.
- Organ distribution of microfilariae was similar between resistant and susceptible strains.
- Adoptive transfer of immune cells or sera did not alter infection duration.
Conclusions:
- Host genetics profoundly influences Brugia malayi microfilariae susceptibility in mice.
- Genetic resistance is primarily determined by a few dominantly inherited genes, independent of the H-2 complex.
- The observed differences in susceptibility are not explained by antibody levels, organ distribution, or cell/serum mediated immunity alone.