Host defense against multicellular, extracellular pathogens such as nematode parasites is believed to be mediated largely, if not exclusively, by T lymphocytes. During our investigations into the course of Brugia malayi and Brugia pahangi infections in immunodeficient mouse models, we found that mice lacking B lymphocytes were permissive for Brugian infections, whereas immunocompetent mice were uniformly resistant. Mice bearing the Btkxid mutation were as permissive as those lacking all B cells, suggesting that the B1 subset may be responsible for host protection. Reconstitution of immunodeficient recombination activating gene (Rag)-1−/− mice with B1 B cells conferred resistance, even in the absence of conventional B2 lymphocytes and most T cells. These results suggest that B1 B cells are necessary to mediate host resistance to Brugian infection. Our data are consistent with a model wherein early resistance to B. malayi is mediated by humoral immune response, with a significant attrition of the incoming infectious larval load. Sterile clearance of the remaining parasite burden appears to require cell-mediated immunity. These data raise the possibility that the identification of molecule(s) recognized by humoral immune mechanisms might help generate prophylactic vaccines.

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A new strain of Babesia microti (KR-1) was isolated from a Connecticut resident with babesiosis by hamster inoculation and adapted to C3H/HeJ and BALB/c mice. To examine the relative importance of humoral and cellular immunity for the control of B. microti infection, we compared the course of disease in wild-type BALB/c mice with that in BALB/c SCID mice, JHD-null (B-cell-deficient) mice, and T-cell receptor ␣␤ (TCR␤ ؊/؊ ) or gamma interferon (IFN-␥) (IFN-␥ ؊/؊ ) knockout mice following inoculation with the KR-1-strain. SCID mice and TCR␣␤ knockouts sustained a severe but nonlethal parasitemia averaging 35 to 45% infected erythrocytes. IFN-␥-deficient mice developed a less severe parasitemia but were able to clear the infection. In contrast, in six of eight JHD-null mice, the levels of parasitemia were indistinguishable from those in the wild-type animals. These data indicate that cellular immunity is critical for the clearance of B. microti in BALB/c mice but that disease resolution can occur even in the absence of IFN-␥.

The nematode parasites Wuchereria bancrofti, Brugia malayi, and B. timori cause a disease in humans known as lymphatic filariasis, which afflicts approximately 120 million people worldwide. The parasites enter the human host from the mosquito either as L3 or as infective larvae and subsequently differentiate through 2 molts. In this article, we show that B. malayi depends on an exogenous source of vitamin C to complete the L3 to L4 molt, a critical morphogenic step in its life cycle. Brugia malayi apparently belongs to a small group of living organisms that depend on an exogenous source of vitamin C. This group includes only primates (including man) and guinea pigs among mammals.

Lymphatic filariasis is a tropical disease caused by the nematode parasitesLymphatic filariasis, a major public health problem in 80 tropical countries, affects 120 million people and is caused by Wuchereria bancrofti, which accounts for 90% of the infections, and Brugia malayi, which causes the remaining 10% (2). Both parasite species have complex life cycles which require vertebrate and mammalian hosts and, similar to other nematodes, must complete distinct developmental stages which are separated by molting events. Human infection is initiated when infective third-stage larvae (henceforth, L3) are deposited onto the skin of a human host by an infected mosquito during a blood meal. The L3 crawl subcutaneously through the bite wound and migrate to the lymphatics, where the parasites live through all the mammalian stages of the life cycle.In the laboratory setting, murine infections with B. malayi or the closely related parasite Brugia pahangi have been used extensively over the past 10 years to study host-parasite interactions. Although the original studies of brugian infection in mice used the subcutaneous route of infection, it was later discovered that intraperitoneal (i.p.) infections with B. pahangi L3 allowed more accurate determinations of worm burdens (19). When injected i.p., the parasites develop normally and infection progresses to patency in permissive hosts with similar kinetics to mosquito-transmitted infection. Moreover, the parasites remain in the peritoneal cavity and can be easily recovered by peritoneal lavage (8). This method has been widely accepted for the study of filarial biology and host-parasite interactions.Normal immunocompetent inbred C57BL/6 and BALB/ cByJ mice are refractory to infection with brugian parasites. However, infection develops to patency in immunodeficient scid/scid or RAG-1 Ϫ/Ϫ mice that lack an adaptive immune system (20). This suggests that mice can support the normal development of these organisms and that immunocompetent mice are able to actively clear the infection due to an efficient immune response. Studies using T-cell-deficient NUDE mice with B. malayi or B. pahangi demonstrated that these mice develop patent infection and harbor parasites as late as 240 days postinfection (28,29,31,33,34). Furthermore, the susceptibility of NUDE mice to B. pahangi infection was reversed by immune reconstitution with neonatal thymocytes from wildtype syngeneic mice or by implantation of neonatal thymus grafts several weeks prior to infection (32).Our previous studies demonstrated a role for B lymphocytes in protection against Brugia infection and the potential of naïve peritoneal cells to transfer this protection to immunodeficient mice (22). In this communication we report the transfer of protection against B. pahangi to T-cell-deficient mice with primed purified peritoneal B lymphocytes and analyze possible mechanisms of B-cell-mediated protection against infection. MATERIALS AND METHODSMice. All mice used in this study were young adult males. The mouse strains that were us...