Maternal influence on susceptibility of offspring to Brugia malayi infection in a murine model of filariasis.

Abstract 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% ( 34 85 ) of the immunocompetent offspring of C.B-17- scid / scid females × 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 .