Experimental Parasitology 93, 120–122 (1999) Article ID expr.1999.4447, available online at http://www.idealibrary.com on RESEARCH BRIEF Life and Death of Brugia malayi in the Mammalian Host: Passive Death vs Active Killing T. V. Rajan, 1 Subash Babu, Deborah Sardinha, Heidi Smith, Lisa Ganley, Natalia Paciorkowski, and Patricia Porte Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut 06030, U.S.A. Rajan, T. V., Babu, S., Sardinha, D., Smith, H., Ganley, L., Pacior- mammalian host. By this period, the infective larvae have positioned kowski, N., and Porte, P. 1999. Life and death of Brugia malayi in themselves in the lymphatic channels. Further differentiation and matu- the mammalian host: passive death vs active killing. Experimental ration to the adult takes place over the next month in the case of B. Parasitology 93, 120–122.  1999 Academic Press malayi and over several months for W. bancrofti. Most common inbred laboratory mice are nonpermissive to B. malayi infection, as indicated by the failure to recover adult worms or microfi- lariae after infection with L3 (Carlow and Philipp 1987). However, these late events in infection do not fully describe the complexity of the B. malayi –host interaction. In order to examine the course of B. Human lymphatic filariasis is caused by two organisms, Wuchereria malayi infection in various mouse strains, we injected cohorts of 25 bancrofti, which occurs throughout the world, and Brugia malayi, BALB/cByJ or C57BL/6J mice with B. malayi L3 and necropsied which is found primarily in Indonesia and Malaysia. While there are batches of 5 mice of each stain weekly, starting 14 days after injection. many differences between these two organisms, there are also many The data for L4 or adult worm recoveries at 2 and 6 weeks postinfection, fundamental areas of similarity. This discussion of the early biology respectively, are shown in Table I. Thus, at least in these two commonly of lymphatic filarial infection will deal primarily with B. malayi since used murine backgrounds, the kinetics of worm recovery shows a it lends itself to laboratory analysis in experimental animal models; divergence between the immunodeficient and the competent counter- however, the basic principles developed here probably also apply to parts past the second week of infection. The former shows a stable W. bancrofti. yield of worms with time, with worm recoveries that are comparable Human infection with these organisms begins when the infected between weeks 2 and 6. On the other hand, the latter progressively mosquito deposits infective-stage (L3) larvae on the skin of the subject. eliminate the worms, until essentially the entire challenge infection is The L3 crawl into the subcutaneous tissues at the site of the puncture eliminated by 6 weeks, except in rare instances. Data from Hayashi and migrate toward a lymphatic channel. The mechanisms by which et al. using BALB/cByJ and BALB/c-nu/nu mice are consistent with the larvae seek, recognize, and colonize the lymphatics are unknown. these data (Hayashi et al. 1989). They found that both BALB/c and Human filarial parasites injected into compatible animal hosts likewise BALB/c-nu/nu mice had comparable worm burdens at 2 weeks (57.2% home to the lymphatics in these atypical hosts (Vickery et al. 1985;  7.5 and 61.2%  6.3, respectively.) They also found that that Hines et al. 1989; Nelson et al. 1991). This observation suggests that 30–50% of injected L3 were recoverable as L4 at 2 weeks in other there is a commonality to the signals that denote the lymphatics as inbred strains (C57BL, DDD, and C3H/HeJ); they did not investigate such in various mammalian species and that the cognate receptors in the immunodeficient counterparts in these other strains. It would appear the filarial nematodes are able to recognize these signals. Molting from that most common inbred strains are permissive for the development the infective L3 stage to the L4 stage occurs after 8–11 days in the of B. malayi to the L4 stage, allowing about half of the injected L3 to mature up to this point. The background commonly used to generate targeted mutations, namely the (129  C57BL/6J) F2, may be different, 1 To whom correspondence should be addressed. Fax (860) 679- 2936. E-mail: rajan@cortex.uchc.edu. since it seems to have low worm burdens even at this early time point 0014-4894/99 $30.00 120 Copyright  1999 by Academic Press All rights of reproduction in any form reserved.