Brugia phangi: effects of third stage larvae ES immunization on early migration and parasite establishment in Mongolian gerbils (Meriones unguiculatus)

Abstract

Brugia infections occur via the bite of an infected mosquito. Third stage infective larvae (L3) deposited on the skin during feeding migrate into the bite wound, through skin and into the lymphatic system. It is hypothesized that L3 excretory/secretory products (ES) are important in this initial phase of the infection. A model for these early migrations has been established by inoculating L3s into the dermis (ID) of the permissive gerbil host. In this model, most L3s injected ID in the louer hind limb travel to the popliteal lymph node by 3 days post infection. Adult parasites are located primarily in the spermatic cord lymphatics by 28 days post infection. L3s injected into the peritoneal cavity (IP) do not migrate, thus ES may play a different role in these infections. Knowledge is lacking on the role of L3 ES in B. pahangi migration and establishment. Proteins in 24 hour L3 ES may facilitate early L3 migration and antibodies to ES may inhibit migration and/or worm establishment. Migration inhibition was assayed in vivo by immunizing gerbils with either 24 hour L3 ES in RIBI adjuvant or RIBI alone. Gerbils were subsequently challenged either ID or IP with 100 L3s and euthanized at 3 and 106 days post infection. Western blot analysis indicates that antibodies in prechallenge sera are produced against ES and share homology with antigens in other B. pahangi stages. ES immunization increased L3 recovery in both ID and IP infected animals at 3DPI. No difference was noted at 106DPI. ES immunization also reduced L3 migration in ID infected gerbils at 3DPI. At 106DPI, immunized animals showed fewer circulating microfilaria and intralymphatic thrombi. At 3DPI, the increase in worm recoveries following immunization may be associated with a decrease in larval migration. The results also suggest that antibody to ES is insufficient to provide protection at both 3DPI and 106DPI. Nonetheless, this response appears to limit the fecundity of adult worms and subsequent formation of intralymphatic thrombi.