HOST NK CELLS ARE REQUIRED FOR THE GROWTH OF THE HUMAN FILARIAL PARASITE BRUGIA-MALAYI IN MICE

Human lymphatic filariasis, which afflicts an estimated 120 million pe ople worldwide, is caused by the large nematode parasites Wuchereria b ancrofti and Brugia malayi. Filarial nematodes require both an arthrop od vector and a mammalian host to complete their life cycle. Within th e definitive (mammalian) host, the lymphatic filarial parasites reside in the lymph nodes and lymphatics, a seemingly hostile environment fo r infectious agents, since the location exposes them to the immune def enses of the host. We present data here that suggest that the growth o f B, malayi in the mammalian host is dependent on host NK cell functio n. Comparisons of worm survival and development in different strains o f mice with varying levels of NK cell activity reveal that NOD/LtSz-sc id/scid and NOD/LtSz-scid/scid B2m(null) mice (with diminished to abse nt NK cell activity respectively), are nonpermissive to worm growth, w hile C.B-17-scid/scid mice with normal NK cell activity are highly per missive. Depletion of NK cells in the permissive C57BL/6J-scid/scid mi ce renders them nonpermissive to B, malayi growth, whereas stimulation of NK cells in NOD/LtSz-scid/scid mice makes them permissive. Tg epsi lon 26 mice, which lack NK and T cells, are nonpermissive, but, when r econstituted with NK; cells by adoptive transfer of bone marrow cells from C57BL/6J-scid/scid mice, are rendered permissive. This requiremen t for NK;cell activity may explain the site specificity of these paras ites, Furthermore, these data suggest that the interaction of the host immune system with the filarial parasite is double edged, with both h ost protective and parasite growth-promoting activities emanating from the former.