[PubMed] [Google Scholar] 12. growth Cyclopamine of pleural leukocyte infiltration were seen in the resistant C57BL/6 mice, explaining the damage of worms later on. Our results suggest that events early in the infection determine susceptibility or resistance to subsequent microfilarial production and a parasite strategy to use specific immune responses to its own benefit. In areas where filariasis is definitely endemic, a small proportion of the population ( 5%) consistently shows neither microfilariae nor pathology. Characterization of the protecting mechanisms operating with this putatively immune population is highly desirable and offers as a result received great attention (18, 23, 41, 46, 47, 50). However, experimental investigations or field observations aiming to correlate parasitological, immunological, and genetic factors with resistance in humans are limited for obvious ethical reasons. The filaria offers proven to be a good murine model (1, 8, 42), since in various strains Cyclopamine of mice it mimics the spectrum of parasitological end result of human being filariasis (42). Recently, genetically altered mice have been used to rapidly determine important immune parts; the absence of Th2 (28, 48, 49) or Th1 (gamma interferon [IFN-]) (44) cytokines as well as of B cells and antibodies (2, 35) offers been shown to modify development or survival, as observed in the nonpermissive models (6, 14, 27, 43). However, the inherent physiological and immunological artifacts that can happen in deficient mice sometimes limit the interpretation of the results. Two previous studies compared the splenic and antibody reactions to in genetically undamaged vulnerable BALB/c mice to the people in resistant B10D2 (33) or C57BL/6 (28) mice. No obvious differences were observed in Cyclopamine the 1st study, and a late stronger Th2 bias characterized the vulnerable mice in the second study. We focused on local processes occurring during the 1st month Cyclopamine of illness as infective larvae are inoculated in the host’s subcutaneous cells and then enter the lymphatic system and migrate to the TNFAIP3 pleural cavity, where they grow and sexually adult (34, 51). We used the permissive BALB/c mice, in which the patent phase begins 55 to 60 days postinoculation, and the C57BL/6 mice, in which filariae are gradually encysted and damaged from day time 40 postinfection (D40 p.i.) onwards, therefore generating no microfilariae (28). We monitored parasitological and immunological features in three compartments: the draining lymph nodes, which until now have not been studied with this filaria; the pleural cavity; and the peripheral blood. The parasitological guidelines included the duration of lymphatic migration; the number of recovered live filariae and their size, stage, and sex as assessed by morphological heroes; and the presence of pleural granulomas. The immune reactions of the mice were assessed by characterizing the leukocyte populations and their proliferation and the production of type 1 and 2 cytokines, antibodies, and the chemokine eotaxin as the filarial development progresses. MATERIALS AND METHODS Filariae, mice, parasite components, and illness protocols. The filaria as previously explained (16). Water-soluble parasite components as a source of antigenic components were processed from homogenized and sonicated infective larvae or adults (Ad). After centrifugation, the supernatant was collected and freezing at ?70C until further use. Protein content material was determined by the Bradford method (Bio-Rad Laboratories, Hercules, CA). Six- to 7-week-old woman BALB/cAnNHsd and C57BL/6NHsd mice were purchased from Harlan Olac (Gannat, France). All mice were managed in microisolators with filter-topped cages and received sterilized food and water to avoid any exposure to other microorganisms, particularly gastrointestinal nematodes such as pinworms, which are known to share antigenic molecules with filariae (26). Mice were injected with 40 L3 in 200 l of RPMI 1640 subcutaneously into the right lumbar area. All experiments and.