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 mous e to investigate the influences of maternal immune status and parasite burden on the susceptibility (or resistance) of offspring to infectio n with the human filarial parasite, Brugia malayi. C.B-l7-scid/scid mi ce 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 malqyi. 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 know n to produce patent infection in > 95% of C.B-17-scid/scid mice. We ob served that 40.0% (34/85) of the immunocompetent offspring of C.B-17-s cid/scid females x C.B-I7-+/+ males were permissive for the growth and development of Brugia malayi larvae to adults. No difference was obse rved in susceptibility to infection between the progeny of infected or uninfected C.B-17-scidlscid mothers mated with C.B-17- +/+ fathers, a rguing against acquired immunological tolerance to the parasite in the former. In marked contrast, only 4.8% (2/42) of the heterozygous prog eny of wild type C.B-I7-+/+ females mated with C.B-17-scidlscid males were permissive. These observations document conversion of a 'resistan t' phenotype to a 'susceptible' phenotype by manipulation of maternal immune status and provide clear evidence of maternal influence on offs pring susceptibility to infection with Brugia malayi.