Differences in Cytokine Responses to<i>Onchocerca volvulus</i>Extract and Recombinant Ov33 and OvL3–1 Proteins in Exposed Subjects with Various Parasitologic and Clinical States

Brattig, Norbert W.; Nietz, Carola; S, Hounkpatin; Lucius, Richard; Seeber, Frank; Pichlmeier, Uwe; Pogonka, Thomas

doi:10.1086/517317

Cited by 32 publications

(26 citation statements)

References 2 publications

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“…With the exception of the IgG4 response to L3 (r ϭ 0.224; P ϭ 0.044; n ϭ 81), there were no significant correlations between levels of IgG antibodies and skin mf counts. IgG2 analysis was excluded in this study because this isotype predominantly recognizes crossreacting phospholipids and carbohydrates (3,12). Interestingly, when the antibody response against rOv-ALT-1 was analyzed, significant increases with age were seen for the IgG1 (r ϭ 0.256; P ϭ 0.048) and IgG3 (r ϭ 0.279; P ϭ 0.031) levels, whereas the IgG4 levels in response to rOv-ALT-1 were almost uniformly low, regardless of age.…”

Section: Resultsmentioning

confidence: 99%

“…Antibody responses in onchocerciasis were analyzed in earlier studies with adult worm extracts (2,6,37,43) or recombinant O. volvulus antigens with or without adult worm extracts (3,18,20,40,42,45). However, with the exception of one recent study (16), none analyzed responses to larva-specific antigens as a function of duration of exposure to O. volvulus.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2002

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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 granulocytemacrophage 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.The filarial parasite Onchocerca volvulus infects about 18 million people, and a further 100 million live in areas in which O. volvulus is endemic in Africa and Latin America. The resulting disease, onchocerciasis, is characterized by severe dermatitis and blindness (21). There is epidemiological evidence that acquired immunity against O. volvulus infection occurs in humans. 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). It has been suggested that the means of limiting acquired infections is through concomitant immunity (36), whereby newly introduced infective-stage larvae (third-stage larvae [L3]) are eliminated ...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2002

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“…In onchocerciasis, the role of IL-10 has been shown to contrast that of IL-4 (10). Thus, patients with a typical Th2 cytokine response to nematode Ag successfully control worm load, but present severe symptoms (10,35,48). It has also been shown for human filariasis and other helminth infections that the asymptomatic carriers have higher IgG4 levels than the patients with chronic disease (10,16,34).…”

Section: Discussionmentioning

confidence: 98%

T Regulatory-1 Cells Induce IgG4 Production by B Cells: Role of IL-10

Satoguina

Weyand

Larbi

et al. 2005

The Journal of Immunology

160

122

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The study was aimed to find out whether T cells with a regulatory profile could regulate the secretion of IgG4. Using tetanus Ag we found that PBMC of healthy human donors responded to exogenous IL-10 by down-regulating IgG1 and increasing IgG4 secretion. IgE was not affected. To investigate the direct effect of IL-10-producing T cells on B cells, we generated T cell clones (TCC) with two different cytokine profiles: first, IL-10high, IL-2low, IL-4low TCC, and second, IL-10low, IL-2high, IL-4high. The T cell-dependent Ab secretion was measured by coculturing purified CD19+ B cells and the TCC. Interestingly, we found that IgG4 production in the coculture correlated with the TCC production of IL-10 (r2 = 0.352, p = 0.0001), but not with IL-2, IL-4, nor IFN-γ. IgE showed only a trend with regard to IL-4. Further, there was decreased Ab secretion in the absence of T-B cell contact. IL-10 also induced IgG4 when added to a Th1 TCC-B cell coculture system. The present study thus shows that in T-B cell coculture, IL-10, if induced by the TCC or added to the system, down-regulates the immune response by inducing IgG4 secretion. This establishes a direct implication of IL-10 in humoral hyporesponsiveness, particularly in compartments where the T-B cell interplay determines the subsequent immune response. The correlation between IgG4 and IL-10 (r2 = 0.352) indicates that IL-10 is an important but not the only factor for IgG4 induction.

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“…Sera from the 18 onchocerciasis patients described above and from 2 healthy European volunteers were analyzed for the presence of Abs specific for WSP and Ags present in the O. volvulus extract, respectively, using an ELISA (26). Briefly, multiple dilutions of the sera were used in Ag-coated microtiter plates and human class-and subclass-specific mAbs (for IgG1, clone NL16; IgG4, clone RJ4 and IgE, clone CIA-A-7.12; Calbiochem, La Jolla, CA) were applied.…”

Section: Ab Analysismentioning

confidence: 99%

The Major Surface Protein of Wolbachia Endosymbionts in Filarial Nematodes Elicits Immune Responses through TLR2 and TLR4

Brattig

Bazzocchi

Kirschning

et al. 2004

The Journal of Immunology

187

173

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More than 150 million humans in tropical countries are infected by filarial nematodes which harbor intracellular bacterial endosymbionts of the genus Wolbachia (Rickettsiales). These bacteria have been implicated in adverse effects of drug treatment in filariasis. The present study provides evidence that purified major Wolbachia surface protein (rWSP) acts as an inducer of the innate immune system through TLR2 and TLR4: 1) recombinant, stringently purified rWSP elicited the release of TNF-α, IL-12, and IL-8 from cultured blood cells of both Onchocerca volvulus-infected and uninfected people; 2) the inflammatory response to rWSP challenge was TLR2- and TLR4-dependent as demonstrated with TLR-transfected fibroblastoid cells, as well as macrophages and dendritic cells from functional TLR-deficient mice; 3) blood cells of onchocerciasis patients exposed to rWSP also generated down-regulating mediators IL-10 and PGE2 after 6 days of culture; 4) furthermore, rWSP-reactive IgG1 Abs were present in sera of O. volvulus-infected people but not in those of uninfected Europeans. The lack of rWSP-reactive IgE and IgG4 in serum indicated a bias toward a Th1-type adaptive immune response. Abs against rWSP stained endobacteria in living and degenerating adult O. volvulus filariae, tissue microfilariae and host tissue macrophages that apparently had engulfed microfilariae. Thus, filarial helminths, through products of their endobacteria such as WSP, acquire characteristics of a typical microbial pathogen inducing immune responses via TLR2 and TLR4.

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Differences in Cytokine Responses toOnchocerca volvulusExtract and Recombinant Ov33 and OvL3–1 Proteins in Exposed Subjects with Various Parasitologic and Clinical States

Cited by 32 publications

References 2 publications

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

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

T Regulatory-1 Cells Induce IgG4 Production by B Cells: Role of IL-10

The Major Surface Protein of Wolbachia Endosymbionts in Filarial Nematodes Elicits Immune Responses through TLR2 and TLR4

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