MacDonald Angus J, Turaga Prasad S D, Harmon-Brown Carolyn, Tierney Tracy J, Bennett Kristine E, McCarthy Maggie C, Simonek Scott C, Enyong Peter A, Moukatte Daniel W, Lustigman Sara
Laboratory of Molecular Parasitology, New York Blood Center, New York, New York 10021, USA.
Infect Immun. 2002 Jun;70(6):2796-804. doi: 10.1128/IAI.70.6.2796-2804.2002.
The possibility of concomitant immunity and its potential mechanisms in Onchocerca volvulus infection were examined by analyzing cytokine and antibody responses to infective larval (third-stage larvae [L3] and molting L3 [mL3]), adult female worm (F-OvAg), and skin microfilaria (Smf) antigens in infected individuals in a region of hyperendemicity in Cameroon as a function of age. Peripheral blood mononuclear cell interleukin 5 (IL-5) responses to F-OvAg and Smf declined significantly with age (equivalent to years of exposure to O. volvulus). In contrast, IL-5 secretion in response to L3 and mL3 remained elevated with increasing age. Gamma interferon responses to L3, mL3, and F-OvAg were low or suppressed and unrelated to age, except for responses to Smf in older subjects. IL-10 levels were uniformly elevated, regardless of age, in response to L3, mL3, and F-OvAg but not to Smf, for which levels declined with age. A total of 49 to 60% of subjects had granulocyte-macrophage colony-stimulating factor responses to all O. volvulus antigens unrelated to age. Analysis of levels of stage-specific immunoglobulin G3 (IgG3) and IgE revealed a striking, age-dependent dissociation between antibody responses to larval antigens (L3 and a recombinant L3-specific protein, O. volvulus ALT-1) which were significantly increased or maintained with age and antibody responses to F-OvAg, which decreased. Levels of IgG1 to L3 and F-OvAg were elevated regardless of age, and levels of IgG4 increased significantly with age, although not to O. volvulus ALT-1, which may have unique L3-specific epitopes. Immunofluorescence staining of whole larvae showed that total anti-L3 immunoglobulin levels also increased with the age of the serum donor. The separate and distinct cytokine and antibody responses to adult and infective larval stages of O. volvulus which are age related are consistent with the acquisition of concomitant immunity in infected individuals.
通过分析喀麦隆高度流行区感染个体针对感染性幼虫（第三期幼虫[L3]和蜕皮L3[mL3]）、成年雌虫（F-OvAg）和皮肤微丝蚴（Smf）抗原的细胞因子和抗体反应，作为年龄的函数，研究了盘尾丝虫感染中伴随免疫的可能性及其潜在机制。外周血单核细胞白细胞介素5（IL-5）对F-OvAg和Smf的反应随年龄显著下降（相当于接触盘尾丝虫的年数）。相比之下，随着年龄增长，对L3和mL3的IL-5分泌仍保持升高。除老年受试者对Smf的反应外，对L3、mL3和F-OvAg的γ干扰素反应较低或受到抑制，且与年龄无关。无论年龄大小，对L3、mL3和F-OvAg的反应中IL-10水平均一致升高，但对Smf的反应中IL-10水平随年龄下降。共有49%至60%的受试者对所有盘尾丝虫抗原的粒细胞巨噬细胞集落刺激因子反应与年龄无关。对阶段特异性免疫球蛋白G3（IgG3）和IgE水平的分析显示，对幼虫抗原（L3和重组L3特异性蛋白，盘尾丝虫ALT-1）的抗体反应与对F-OvAg的抗体反应之间存在显著的、年龄依赖性的分离，前者随年龄显著增加或维持，而后者则下降。无论年龄大小，IgG1对L3和F-OvAg的水平均升高，IgG4水平随年龄显著增加，尽管对盘尾丝虫ALT-1不增加，盘尾丝虫ALT-1可能具有独特的L3特异性表位。全幼虫的免疫荧光染色显示，总的抗L3免疫球蛋白水平也随血清供体年龄的增加而增加。盘尾丝虫成虫和感染性幼虫阶段与年龄相关的单独且不同的细胞因子和抗体反应与感染个体中伴随免疫的获得一致。
