Maternal influence on susceptibility of offspring to Brugia malayi infection in a murine model of filariasis.
We have used the severe combined immunodeficient C.B-17-scid/scid mouse to investigate the influences of maternal immune status and parasite burden on the susceptibility (or resistance) of offspring to infection with the human filarial parasite, Brugia malayi. C.B-17-scid/scid mice are permissive for infection while immunocompetent C.B-17(-)+/+ mice are uniformly resistant. Reciprocal matings of C.B-17-scid/scid and C.B-17(-)+/+ mice were performed. The C.B-17-scid/scid females were either naive or infected with Brugia malayi. The resulting immunocompetent C.B-17-scid/+ and C.B-17(-)+/scid progeny were challenged at weaning with an intraperitoneal injection of Brugia malayi third stage larvae known to produce patent infection in > 95% of C.B-17-scid/scid mice. We observed that 40.0%l (34/85) of the immunocompetent offspring of C.B-17-scid/scid females x C.B-17(-)+/+ males were permissive for the growth and development of Brugia malayi larvae to adults. No difference was observed in susceptibility to infection between the progeny of infected or uninfected C.B-17-scid/scid mothers mated with C.B-17(-)+/+ fathers, arguing against acquired immunological tolerance to the parasite in the former. In marked contrast, only 4.8% (2/42) of the heterozygous progeny of wild type C.B-17(-)+/+ females mated with C.B-17-scid/scid males were permissive. These observations document conversion of a 'resistant' phenotype to a 'susceptible' phenotype by manipulation of maternal immune status and provide clear evidence of maternal influence on offspring susceptibility to infection with Brugia malayi.
Rajan
T V
TV
Department of Pathology, University of Connecticut Health Center, Farmington 06030.
Bailis
J M
JM
Yates
J A
JA
Shultz
L D
LD
Greiner
D L
DL
Nelson
F K
FK
D000483:Alleles; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D017178:Brugia malayi / Q000276:immunology; D005260:Female; D005368:Filariasis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D020022:Genetic Predisposition to Disease; D007112:Immunity, Maternally-Acquired / Q000235:genetics*; D008297:Male; D051379:Mice; D016513:Mice, SCID