Immunity to Onchocerciasis: Cells from Putatively Immune Individuals Produce Enhanced Levels of Interleukin-5, Gamma Interferon, and Granulocyte-Macrophage Colony-Stimulating Factor in Response toOnchocerca volvulusLarval and Male Worm Antigens

Abstract

Antigen-specific interleukin-5 (IL-5), gamma interferon (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) responses in individuals living in an area of hyperendemicity for onchocerciasis in Cameroon were examined. The responses against antigens prepared from Onchocerca volvulus third-stage larvae (L3), molting L3 (mL3), and crude extract from adult males (M-OvAg) were compared to the responses against antigens from adult female worms and skin microfilariae. Cytokine responses for the putatively immune individuals (PI) and the infected individuals (INF) were compared. A differential cytokine profile of IL-5 (Th2 phenotype) and IFN-gamma (Th1 phenotype) was found in these individuals in response to the antigens. In both the PI and the INF, Th2 responses against all the antigens tested were dominant. However, in the PI group as a whole, there was an enhanced Th2 response against the larval antigens and the adult male and adult female antigens, and a Th1 response in a subgroup of the PI (27 to 54.5%) against L3, mL3, and M-OvAg antigens was present. While the PI produced significantly higher levels of GM-CSF against L3, mL3, and M-OvAg antigens than the INF, there was no difference in the GM-CSF responses of the groups against the other antigens. The present study indicated that, in comparison to the INF, the PI have distinct larva-specific and adult male-specific cytokine responses, thus supporting the premise that immunological studies of the PI would lead to the identification of immune mechanisms and the target genes that play a role in protective immunity.

Protective Immunity to the Larval Stages ofOnchocerca volvulusIs Dependent on Toll-Like Receptor 4

“…Larvae, recovered after 1 or 2 days in culture, and adult female worms, obtained at the Tropical Medicine Research Station, Kumba, Cameroon, were quick-frozen in liquid nitrogen. Soluble antigens were prepared as previously described (35). Briefly, the worms were ground to a powder using a Bessman tissue pulverizer (Spectrum Lab Products, Houston, Tex.)…”

“…Individual immune responses appear to be responsible for the different disease states, and roles have been ascribed for T helper 1 (Th1) cells, Th2 cells, antibodies, and granulocytes in the different disease presentations (15). Immunity against O. volvulus in putatively immune individuals has been associated with the development of a Th2 response to larval and adult antigens, with a subgroup producing a Th1 response (35). Additionally, the immune response after early exposure to O. volvulus was found to be a mixed Th1/Th2 response (8).…”

Differential Cytokine and Antibody Responses to Adult and Larval Stages ofOnchocerca volvulusConsistent with the Development of Concomitant Immunity

“…Crude L3, mL3, adult female worm (F-OvAg), and skin microfilaria (Smf) antigens were prepared as described before (46). Briefly, the worms were ground to a powder by using a Bessman tissue pulverizer (Spectrum Lab Products, Houston, Tex.)…”

“…Antigens from L3 and subsequent developmental stages of molting L3 (mL3) have been shown to be promising sources for protective antigens and targets for the control of filarial infections (8,13,30). It was previously shown that PI individuals express enhanced Th2 and Th1 responses to larval antigens (46); however, the mechanisms that may allow INF individuals to limit new infections are not known.…”

“…For example, in regions of high endemicity, despite constant exposure to infected Simulium flies, 1 to 5% of the population exhibits no clinical manifestations of disease. These individuals are considered to be immune to infection and are referred to as putatively immune (PI) (15,17,46,47). Furthermore, in chronically infected (INF) individuals, the number of skin microfilariae (mf) tends to level off between the ages of 20 and 40 years, suggesting that these individuals have developed a means of limiting acquired infections (11).…”