Induction of CD4+CD25+FOXP3+ Regulatory T Cells during Human Hookworm Infection Modulates Antigen-Mediated Lymphocyte Proliferation

Hookworm infection is considered one of the most important poverty-promoting neglected tropical diseases, infecting 576 to 740 million people worldwide, especially in the tropics and subtropics. These blood-feeding nematodes have a remarkable ability to downmodulate the host immune response, protecting themselves from elimination and minimizing severe host pathology. While several mechanisms may be involved in the immunomodulation by parasitic infection, experimental evidences have pointed toward the possible involvement of regulatory T cells (Tregs) in downregulating effector T-cell responses upon chronic infection. However, the role of Tregs cells in human hookworm infection is still poorly understood and has not been addressed yet. In the current study we observed an augmentation of circulating CD4+CD25+FOXP3+ regulatory T cells in hookworm-infected individuals compared with healthy non-infected donors. We have also demonstrated that infected individuals present higher levels of circulating Treg cells expressing CTLA-4, GITR, IL-10, TGF-β and IL-17. Moreover, we showed that hookworm crude antigen stimulation reduces the number of CD4+CD25+FOXP3+ T regulatory cells co-expressing IL-17 in infected individuals. Finally, PBMCs from infected individuals pulsed with excreted/secreted products or hookworm crude antigens presented an impaired cellular proliferation, which was partially augmented by the depletion of Treg cells. Our results suggest that Treg cells may play an important role in hookworm-induced immunosuppression, contributing to the longevity of hookworm survival in infected people

Induction of CD4+CD25+FOXP3+ Regulatory T Cells during Human Hookworm Infection Modulates Antigen-Mediated Lymphocyte Proliferation.

Submitted by Nuzia Santos ([email protected]) on 2014-12-02T12:58:23Z No. of bitstreams: 1 Induction of CD4+CD25+FOXP3+ Regulatory T Cells during Human Hookworm Infection Modulates Antigen-Mediated Lymphocyte Proliferation.pdf: 583244 bytes, checksum: 380031abcfa9a222d6ee2c5e979d06ea (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2014-12-02T13:07:36Z (GMT) No. of bitstreams: 1 Induction of CD4+CD25+FOXP3+ Regulatory T Cells during Human Hookworm Infection Modulates Antigen-Mediated Lymphocyte Proliferation.pdf: 583244 bytes, checksum: 380031abcfa9a222d6ee2c5e979d06ea (MD5)Made available in DSpace on 2014-12-02T13:07:36Z (GMT). No. of bitstreams: 1 Induction of CD4+CD25+FOXP3+ Regulatory T Cells during Human Hookworm Infection Modulates Antigen-Mediated Lymphocyte Proliferation.pdf: 583244 bytes, checksum: 380031abcfa9a222d6ee2c5e979d06ea (MD5) Previous issue date: 2011Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Instituto Nacional de Ciencia e Tecnologia em Doenças Tropicais. BrazilUniversidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Hospital das Clínicas. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Instituto Nacional de Ciencia e Tecnologia em Doenças Tropicais. BrazilUniversidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Instituto Nacional de Ciencia e Tecnologia em Doenças Tropicais. BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrasilInstituto Nacional de Ciencia e Tecnologia em Doenças Tropicais. Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrasilInstituto Nacional de Ciencia e Tecnologia em Doenças Tropicais. Brazil/Universidade Federal de Minas Gerais. Escola de Enfermagem. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil/Instituto Nacional de Ciencia e Tecnologia em Doenças Tropicais. Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, BrazilHookworm infection is considered one of the most important poverty-promoting neglected tropical diseases, infecting 576 to 740 million people worldwide, especially in the tropics and subtropics. These blood-feeding nematodes have a remarkable ability to downmodulate the host immune response, protecting themselves from elimination and minimizing severe host pathology. While several mechanisms may be involved in the immunomodulation by parasitic infection, experimental evidences have pointed toward the possible involvement of regulatory T cells (Tregs) in downregulating effector T-cell responses upon chronic infection. However, the role of Tregs cells in human hookworm infection is still poorly understood and has not been addressed yet. In the current study we observed an augmentation of circulating CD4+ CD25+ FOXP3+ regulatory T cells in hookworm-infected individuals compared with healthy non-infected donors. We have also demonstrated that infected individuals present higher levels of circulating Treg cells expressing CTLA-4, GITR, IL-10, TGF-b and IL-17. Moreover, we showed that hookworm crude antigen stimulation reduces the number of CD4+ CD25+ FOXP3+ T regulatory cells co-expressing IL-17 in infected individuals. Finally, PBMCs from infected individuals pulsed with excreted/secreted products or hookworm crude antigens presented an impaired cellular proliferation, which was partially augmented by the depletion of Treg cells. Our results suggest that Treg cells may play an important role in hookworm-induced immunosuppression, contributing to the longevity of hookworm survival in infected people