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NKG2D PROMOTES CD8 T CELL-MEDIATED CYTOTOXICITY AND IS ASSOCIATED WITH TREATMENT FAILURE IN HUMAN CUTANEOUS LEISHMANIASIS
Antígenos CD8
Linfócitos T
Terapêutica
Leishmaniose cutânea
Autor(es)
Afiliação
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Universidade Federal da Bahia. Complexo Hospitalar Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Universidade Federal da Bahia. Complexo Hospitalar Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciências e Tecnologia-Doenças Tropicais. Salvador, BA, Brasil.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Universidade Federal da Bahia. Complexo Hospitalar Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciências e Tecnologia-Doenças Tropicais. Salvador, BA, Brasil.
Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University. Columbus, Ohio, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Universidade Federal da Bahia. Complexo Hospitalar Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Universidade Federal da Bahia. Complexo Hospitalar Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciências e Tecnologia-Doenças Tropicais. Salvador, BA, Brasil.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Universidade Federal da Bahia. Complexo Hospitalar Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciências e Tecnologia-Doenças Tropicais. Salvador, BA, Brasil.
Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University. Columbus, Ohio, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Resumo em Inglês
Cutaneous leishmaniasis exhibits a spectrum of clinical presentations dependent upon the parasites’ persistence and host immunopathologic responses. Although cytolytic CD8 T cells cannot control the parasites, they significantly contribute to pathologic responses. In a murine model of cutaneous leishmaniasis, we previously found that NKG2D plays a role in the ability of cytolytic CD8 T cells to promote disease in leishmanial lesions. Here, we investigated whether NKG2D plays a role in human disease. We found that NKG2D and its ligands were expressed within lesions from L. braziliensis-infected patients and that IL-15 and IL-1β were factors driving NKG2D and NKG2D ligand expression, respectively. Blocking NKG2D reduced degranulation by CD8 T cells in a subset of patients. Additionally, our transcriptional analysis of patients’ lesions found that patients who failed the first round of treatment exhibited higher expression of KLRK1, the gene coding for NKG2D, than those who responded to treatment. These findings suggest that NKG2D may be a promising therapeutic target for ameliorating disease severity in cutaneous leishmaniasis caused by L. braziliensis infection.
DeCS
Subfamília K de Receptores Semelhantes a Lectina de Células NKAntígenos CD8
Linfócitos T
Terapêutica
Leishmaniose cutânea
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