Cutaneous pathology in onchocerciasis associated with pronounced systemic T-helper 2-type responses to Onchocerca volvulus

Timmann, Christian; Abraha, R.S.; Hamelmann, Christoph; Büttner, Dietrich W.; Lepping, B.; Marfo, Yeboah; Brattig, Norbert W.; Horstmann, Rolf D.

doi:10.1046/j.1365-2133.2003.05556.x

Cited by 26 publications

(23 citation statements)

References 16 publications

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“…The reason may well be that, in contrast to the direct effect of LPS on macrophages, the effect of an antigen on IL-10 production by T cells is influenced by a number of variables, including antigen presentation, costimulatory activities, numbers of antigen-reactive Tr1 cells, and possible influences of concomitant infections. 1,23,29 Among these are influences by potentially crossreactive intestinal nematodes, which were found in approximately 70% of the study subjects, 22 whereas individuals concomitantly infested with extraintestinal helminths such as other filariae or schistosomes had been excluded from the study. Finally, TGF and additional members of the IL-10 subfamily, which were not investigated here, may have influenced PBC proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…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. 22 …”

Section: Discussionmentioning

confidence: 99%

“…Approximately one-third of them (115 out of 337) had immunoreactive onchodermatitis, including acute and chronic papular dermatitis, atrophy, and lichenified dermatitis. 22 The proliferation of PBC was studied in whole-blood cultures on stimulation with OvAg or phytohemagglutinin (PHA).…”

Section: Phenotypes Studiedmentioning

confidence: 99%

“…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.…”

Section: Study Populationmentioning

confidence: 99%

“…21 Immunosuppression is marked by high numbers of the larval microfilariae without significant immune reactions, whereas immunopathology is characterized by various forms of immunoreactive dermatitis. 22 A role of IL-10 in onchocerciasis has been documented by showing that T-cell hyporesponsiveness in vitro is reversed by neutralizing antibodies to IL-10. 23 Here, we describe studies of individuals infected with the tissue nematode O. volvulus and show that promoter haplotypes of IL-10 influence in vitro proliferation of PBCs in response to O. volvulus antigen (OvAg).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2004

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Since interleukin (IL)-10 is a key mediator of immunosuppression, and immunosuppression is considered an important element of helminth infection, we studied variants of the putative IL-10 gene promoter in 337 individuals from 130 families heavily exposed to infection by the tissue nematode Onchocerca volvulus. As shown by transmission disequilibrium tests, variants of the IL-10 promoter at positions -1082(G/A), -819(C/T), and -592(C/A) in the haplotype of ATA were significantly associated with high peripheral blood cell (PBC) proliferative responses to O. volvulus antigen (OvAg). No associations were observed using phytohemagglutinin-induced PBC proliferation or with qualitative or quantitative phenotypes of onchocerciasis or onchocerciasis-related skin disease. The findings are compatible with the hypothesis that the ATA haplotype causes a decrease in IL-10 production by OvAg-reactive type-1 regulatory T-lymphocytes, thereby alleviating the suppression of other T cells. To our knowledge, this is the first time that an influence of IL-10 promoter variants is shown on the adaptive immune response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Phenotypes Studiedmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2004

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A Roadmap Followed: The Path Towards the Elimination of Onchocerciasis in Latin America

Rodríguez‐Pérez

Lara-Ramírez

Real-Najarro

et al. 2015

Neglected Tropical Diseases

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Immunohistology of ectopic secondary lymph follicles in subcutaneous nodules from patients with hyperreactive onchocerciasis (sowda)

et al. 2010

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Ectopic secondary lymph follicles emerge in patients with autoimmune or infectious diseases, e.g. in the synovium in rheumatoid arthritis or the skin in Borrelia burgdorferi infection, but ectopic localisations in the skin are rarely described for helminth infections. We investigated the cellular composition of secondary lymph follicles in subcutaneous nodules from eight patients with hyperreactive onchocerciasis (synonymous “localised” form or sowda) using immunohistology. CD3- and CD45RO-positive T cells and CD20-positive B cells were present in the mantle zone. The germinal centre was characterised by many B cells and CD35-positive follicular dendritic cells, which formed a network of attached IgE- and CD23-positive cells with the low-affinity IgE (epsilon) receptor. Few of the B cells were labelled for IgG1, IgG2 and IgG4, whereas in other zones of the nodule IgG1 was expressed by plasma cells and IgG1-coated dead microfilariae. B cells and few macrophages expressed the MHC class II molecule HLA-DR. Mature CD68-positive tingible body macrophages with phagocytosed leukocytes and CD57-positive lymphocytes occurred in the germinal centre. Macrophages in the germinal centre only weakly expressed alpha1-antichymotrypsin in contrast to macrophages in other zones of the onchocercoma. Furthermore, the multifunctional cytokine TGF-beta was only weakly expressed by macrophages and lymphocytes in the secondary follicles. Only few tryptase-positive mast cells, calprotectin-positive young macrophages, eosinophils and neutrophils occurred in the secondary follicles, although these cells were abundant in the onchocercomas. In conclusion, the ectopic secondary lymph follicles in onchocercomas and lymph nodes from hyperreactive onchocerciasis patients are equally composed.Electronic supplementary materialThe online version of this article (doi:10.1007/s00436-010-1912-0) contains supplementary material, which is available to authorized users.

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Cutaneous pathology in onchocerciasis associated with pronounced systemic T-helper 2-type responses to Onchocerca volvulus

Abstract: Skin lesions in onchocerciasis are associated with a spectrum of increasing generalized Th2-type responses ranging from low reactivities in cases of depigmentation alone to strong reactivities in cases of lichenification.

Cited by 26 publications

References 16 publications

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

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

A Roadmap Followed: The Path Towards the Elimination of Onchocerciasis in Latin America

Immunohistology of ectopic secondary lymph follicles in subcutaneous nodules from patients with hyperreactive onchocerciasis (sowda)

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