Onchocerca volvulus–Exposed Persons Fail to Produce Interferon‐γ in Response toO. volvulusAntigen but Mount Proliferative Responses with Interleukin‐5 and IL‐13 Production that Decrease with Increasing Microfilarial Density

Abstract

The cellular immune response to Onchocerca volvulus antigen (OvAg) was studied in 551 persons exposed to O. volvulus transmission in a hyperendemic area of Ghana, West Africa. A whole-blood assay showed that, in response to a soluble O. volvulus extract, cell proliferation, as well as interleukin (IL)-5 and IL-13 concentrations in the supernatants, were high in cultures of blood from microfilaria (mf)-negative persons and significantly decreased with increasing mf counts of the donors. Only background concentrations of interferon (IFN)-gamma were found, and these did not correlate with mf counts. In response to a mitogen, cells from all persons strongly reacted with proliferation and secretion of all 3 cytokines studied. These findings show that the response of human peripheral blood cells to OvAg does not include significant IFN-gamma production; that mf negativity is associated with IL-5 and IL-13 production but not, as previously suggested, with IFN-gamma production; and that IL-5 and IL-13 production decreases with increasing mf density.

Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen

“…In a previous report we have shown, however, that the antigen preparation and conditions employed in our study generated a virtually pure Th2-type of T-cell response, 26 whereas LPS-driven T-cell responses commonly are of the Th1 type. 27 In addition, Doetze et al 23 have shown that T-cell responses in O. volvulus infection include the activation of Tr1 cells, which produce IL-10 and transforming growth factor (TGF) .…”

“…In this context, it is of interest to note that a significant negative correlation was observed between PBC proliferation and microfilaria counts. 26 The lack of an IL-10 association would support the notion that the presence of microfilariae causes a suppression of PBC proliferation and not vice versa, in the sense that a primarily strong (and genetically influenced) PBC response would suppress worm development. Concerning the dermatitis phenotype, the lack of an IL-10 association may be explained by the finding that enhanced Th2-type responses rather than reduced immunosuppressive activities were found associated with the occurrence of skin lesions.…”

“…The study participants were recruited near Dunkwa, Central Region of Ghana, West Africa, in an area hyperendemic for onchocerciasis. 22,26 Study villages and participants were selected for the absence of other filarial infections and schistosomiasis, respectively. 26 Parasitological and immunological methods Skin microfilarial counts were assessed microscopically according to WHO recommendations.…”

“…22,26 Study villages and participants were selected for the absence of other filarial infections and schistosomiasis, respectively. 26 Parasitological and immunological methods Skin microfilarial counts were assessed microscopically according to WHO recommendations. 31 PBC proliferation was determined in ex vivo whole-blood cultures.…”

“…Cell proliferation was determined by the incorporation of [ 3 H]thymidine in cpm as described. 26 Classification of skin changes Skin lesions were classified according to Murdoch et al 32 The clinical entities of acute papular onchodermatitis, chronic papular onchodermatitis, atrophy, and lichenified onchodermatitis were summarized as immunoreactive onchodermatitis. They were found to be characterized by pronounced IgE values, high peripheral blood eosinphil granulocyte counts, and elevated PBC proliferative responses.…”