Infection with parasitic nematodes is characterized by the induction of a profound type 2 immune response. We have studied the role of glycans in the induction of the skewed type 2 response by antigens of the parasitic nematode Brugia malayi as well as the free-living nematode Caenorhabditis elegans. Lymph node cells from BALB/c mice immunized with soluble extracts of the two nematodes showed distinct antigen-specific proliferation and cytokine production; however, both nematodes induced antigen-specific interleukin 4 (IL-4) production, demonstrating that the induction of a biased type 2 response is not unique to parasitic nematodes. Sodium periodate-treated soluble extracts of both nematodes consistently induced significantly less IL-4 production than the respective mock-treated extracts, indicating that glycans play a critical role in the induction of the Th2 immune response by these nematodes. The glycan-dependent induction of the Th2-potentiating cytokine IL-4 occurs by 72 h postinoculation. Our data suggest that glycan determinants common to nematodes act as ligands, displaying distinct molecular patterns that trigger the immune system to launch a biased Th2 immune response upon exposure to these organisms or their products. Further, the similarity of our findings to those for Schistosoma mansoni egg antigen is striking considering the enormous phylogenetic distance between nematodes and trematodes. These data thus have important implications for how the mammalian host responds to widely divergent metazoan invaders and suggest that the powerful C. elegans model system can be used to address these questions.

The impact of concomitant human immunodeficiency virus (HIV) infection on the antibody response of onchocerciasis patients to Onchocerca volvulus antigens (OvAg) was studied by Western blotting and enzyme linked immunosorbent assay (ELISA). Immunoglobulin G (IgG) antibodies in sera from 45 HIV-sero-positive O. volvulus microfilariae (mf) carriers (HIV+/Ov+) recognized significantly fewer distinct O. volvulus antigenic bands, and responded less frequently to all detected bands compared to sera from 61 matched HIV-seronegative mf carriers (HIV-/Ov+). 29% of 31 follow-up sera from the HIV+/Ov+ patients failed to react to many of the antigenic bands recognized by initial sera from the same patients. Among 4 HIV+/Ov+ persons examined for total CD4+ cells, loss of reactivity corresponded with low CD4+ total cell counts. In an OvAg ELISA, sera from the HIV+/Ov+ individuals had significantly lower IgG+IgM antibody levels than sera from the HIV-/Ov+ persons, and the sensitivity of the assay was 87% for the HIV+/Ov+ subjects compared to 100% for those who were HIV-/Ov+. It is concluded that HIV-infected onchocerciasis patients exhibit significantly impaired antibody responses to O. volvulus antigens, and tend to lose their reactivity to these antigens over time due to immune response abnormalities caused by the concomitant HIV infection.

A total detergent-soluble extract of adult female Onchocerca volvulus (OvAg) and a recombinant O. volvulus protein (Ov33) linked to glutathione-S-transferase (GST) were compared with regard to their serodiagnostic suitability for differentiating between O. volvulus and Mansonella perstans infections in a region endemic for both filarial worms in western Uganda. Using OvAg in an enzyme-linked immunosorbent assay (ELISA), 98.8% sensitivity was obtained examining 84 O. volvulus microfilariae (mf) carriers living in the hyperendemic area. However, 5 of 18 (28%) sera from M. perstans mf carriers without O. volvulus mf, from another area hypoendemic for O. volvulus, cross-reacted with OvAg. Using the recombinant antigen Ov33-GST in an ELISA and Western blot assay, sensitivity for O. volvulus remained high (97.2% and 98.8% respectively) while none of 90 sera from M. perstans mf carriers reacted positively. Both antigens were used to examine a batch of sera from 260 persons living in the onchocerciasis hyperendemic area who did not have mf in their skin snips (9.5% of 2728 persons examined); 116 of these sera (44.6%) were positive in the OvAg ELISA, compared to 85 (32.7%) and 69 (26.5%) which were positive in Ov33-GST ELISA and Ov33-GST Western blot, respectively. Reaction with GST alone was minimal. The recombinant antigen Ov33 efficiently differentiates between O. volvulus and M. perstans infections, and is sensitive when used to detect patent and prepatent or low-level O. volvulus infections.

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