Low levels of transforming growth factor-beta (TGF-beta) and reduced suppression of Th2-mediated inflammation in hyperreactive human onchocerciasis.

TY - JOUR

T1 - Low levels of transforming growth factor-beta (TGF-beta) and reduced suppression of Th2-mediated inflammation in hyperreactive human onchocerciasis.

AU - Korten, S

AU - Hoerauf, A

AU - Kaifi, Jussuf

AU - Büttner, D W

PY - 2011

Y1 - 2011

N2 - Th2-biased inflammation with eosinophilia and IgE production is a hallmark of helminth infections. It is pronounced in hyperreactive onchocerciasis patients ('sowda' or 'local form'), who efficiently kill microfilariae resulting in severe dermatitis and lymphadenitis. In contrast, hyporeactive patients ('generalised form') tolerate high microfilarial loads. This is thought to be mediated by regulatory CD4+ T cells and macrophages producing suppressive cytokines such as IL-10 and transforming growth factor-beta (TGF- ). We investigated whether hyperreactivity was reflected by lower local TGF- production, analysing stable latent TGF- 1 expression in onchocercomas, lymph nodes and skin from hyperreactive and hyporeactive patients by immunohistochemistry. TGF- expression was compared with that of IgE, IgG1, IgG4, and the antigen-presenting, CD4+ T cell-inducing MHC class II molecule HLA-DR. TGF- was weakly and less frequently expressed by various cell types in onchocercomas, skin and lymph nodes from hyperreactive compared to hyporeactive patients. This applied to reactions around living and dead adult worms as well as dead microfilariae. Antigen-presenting cells strongly expressed HLA-DR in both forms, but their numbers were reduced in hyperreactive nodules. Plasma cells produced more IgE and IgG1, but less of the anti-inflammatory antibody IgG4 in hyperreactive onchocercomas. In conclusion, hyperreactivity is linked with reduced local expression of TGF- , HLA-DR and IgG4, which might contribute to the insufficient down-regulation of inflammation via TGF- - and HLA-DR-induced regulatory lymphocytes.

AB - Th2-biased inflammation with eosinophilia and IgE production is a hallmark of helminth infections. It is pronounced in hyperreactive onchocerciasis patients ('sowda' or 'local form'), who efficiently kill microfilariae resulting in severe dermatitis and lymphadenitis. In contrast, hyporeactive patients ('generalised form') tolerate high microfilarial loads. This is thought to be mediated by regulatory CD4+ T cells and macrophages producing suppressive cytokines such as IL-10 and transforming growth factor-beta (TGF- ). We investigated whether hyperreactivity was reflected by lower local TGF- production, analysing stable latent TGF- 1 expression in onchocercomas, lymph nodes and skin from hyperreactive and hyporeactive patients by immunohistochemistry. TGF- expression was compared with that of IgE, IgG1, IgG4, and the antigen-presenting, CD4+ T cell-inducing MHC class II molecule HLA-DR. TGF- was weakly and less frequently expressed by various cell types in onchocercomas, skin and lymph nodes from hyperreactive compared to hyporeactive patients. This applied to reactions around living and dead adult worms as well as dead microfilariae. Antigen-presenting cells strongly expressed HLA-DR in both forms, but their numbers were reduced in hyperreactive nodules. Plasma cells produced more IgE and IgG1, but less of the anti-inflammatory antibody IgG4 in hyperreactive onchocercomas. In conclusion, hyperreactivity is linked with reduced local expression of TGF- , HLA-DR and IgG4, which might contribute to the insufficient down-regulation of inflammation via TGF- - and HLA-DR-induced regulatory lymphocytes.

KW - Animals

KW - Humans

KW - Male

KW - Female

KW - Child

KW - Immunoglobulin E immunology

KW - Immunoglobulin G immunology

KW - Antigen-Presenting Cells

KW - HLA-DR Antigens immunology

KW - Host-Parasite Interactions

KW - Liberia

KW - Onchocerca volvulus immunology

KW - Onchocerciasis immunology

KW - Th2 Cells immunology

KW - Transforming Growth Factor beta1 immunology

KW - Yemen

KW - Animals

KW - Humans

KW - Male

KW - Female

KW - Child

KW - Immunoglobulin E immunology

KW - Immunoglobulin G immunology

KW - Antigen-Presenting Cells

KW - HLA-DR Antigens immunology

KW - Host-Parasite Interactions

KW - Liberia

KW - Onchocerca volvulus immunology

KW - Onchocerciasis immunology

KW - Th2 Cells immunology

KW - Transforming Growth Factor beta1 immunology

KW - Yemen

M3 - SCORING: Zeitschriftenaufsatz

VL - 138

SP - 35

EP - 45

JO - PARASITOLOGY

JF - PARASITOLOGY

SN - 0031-1820

IS - 1

M1 - 1

ER -