Cell-adhesion molecules expressed by activated eosinophils in Onchocerca volvulus infection.

Cell-adhesion receptors mediate the interaction between host effector cells and cellular or multicellular targets, including opsonized parasites. Our recent finding of a deposition of plasma proteins, including fibronectin, on the surface of infective larvae of the helminthic parasite Onchocerca volvulus led us to investigate the possible expression of cell-adhesion molecules (CAM), particularly fibronectin receptors, on eosinophilic granulocytes from persons infected with O. volvulus. Immunofluorescence analyses showed that freshly isolated eosinophils strongly expressed the beta 2-integrin CR3 and exhibited to a lower degree CR4 and the integrin-associated carbohydrate determinant Le(x), as well as antigen p24 (CD9). Eosinophils exposed to the eosinophil-active cytokines recombinant human interleukin 3 (rhIL-3) and granulocyte/macrophage colony-stimulating factor (rhGM-CSF) in addition to CR3, CR4, and CD9 expressed the beta 1-integrins VLA-4 and to a lesser extent VL-5 (both fibronectin receptors) as well as the intercellular adhesion molecule ICAM-1. Low-level expression of these adhesins was also observed on eosinophils cultured in the presence of these interleukins on confluent fibroblasts. The presence of VLA-4 as well as VLA-5 on activated eosinophils was confirmed by demonstration of the formation of immune rosettes using antibody-coated microspheres and by their attachment to fibronectin-coated surfaces. These results indicate the possibility of an involvement of previously unidentified antibody- and complement-independent mechanisms in cellular interactions with the parasite O. volvulus.

Strong IgG isotypic antibody response in sowdah type onchocerciasis.

Persons exposed to Onchocerca volvulus express differences in manifestations of onchocerciasis ranging from hyporeactive (generalized) to hyperreactive (sowdah) forms; absence of disease is seen in endemic normal persons. Analysis of the IgG isotypic antibody response to O. volvulus extracts and nonparasite ubiquitous antigens in 92 West Africans revealed highest anti-O. volvulus IgG1 and IgG2 responses in sowdah, high levels in the generalized form, and low antibody levels in endemic normal persons. Nonexposed persons had no antibodies. A significant IgG3 antibody response was detected only in sowdah, while high IgG4 levels occurred in both polar groups but were absent in both control groups. Isotypic responses to antigens unrelated to O. volvulus were similar in all groups but showed higher IgG1 and IgG2 levels in sowdah. Sowdah patients had high levels of Ro/SS-A antibodies, circulating immune complexes, and eosinophil cationic protein. These results document a strong B cell response in African sowdah and indicate variations in immune responsiveness.