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https://www.arca.fiocruz.br/handle/icict/20770
CYTOTOXIC T CELLS MEDIATE PATHOLOGY AND METASTASIS IN CUTANEOUS LEISHMANIASIS
Leishmania braziliensis
Citotoxicidade imunológica
Linfócitos T Citotóxicos
Ratos
Leishmania braziliensis
Cytotoxicity, Immunologic
T-Lymphocytes, Cytotoxic
Mice
Author
Affilliation
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
Universidade Federal da Bahia. Hospital Universitario Prof. Edgard Santos. Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais. Serviço de Imunologia. Salvador, BA, Brasil
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
University of Pennsylvania. Department of Biology. Philadelphia Pennsylvania, USA
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
University of Pennsylvania. Department of Biology. Philadelphia Pennsylvania, USA
University of Pennsylvania. Perelman School of Medicine. Department of Microbiology. Philadelphia, Pennsylvania, USA
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
Fundação Gonçalo Moniz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
Universidade Federal da Bahia. Hospital Universitario Prof. Edgard Santos. Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais. Serviço de Imunologia. Salvador, BA, Brasil
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
University of Pennsylvania. Department of Biology. Philadelphia Pennsylvania, USA
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
University of Pennsylvania. Department of Biology. Philadelphia Pennsylvania, USA
University of Pennsylvania. Perelman School of Medicine. Department of Microbiology. Philadelphia, Pennsylvania, USA
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
Fundação Gonçalo Moniz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
Abstract
Disease progression in response to infection can be strongly influenced by both pathogen burden and infection-induced immunopathology. While current therapeutics focus on augmenting protective immune responses, identifying therapeutics that reduce infection-induced immunopathology are clearly warranted. Despite the apparent protective role for murine CD8⁺ T cells following infection with the intracellular parasite Leishmania, CD8⁺ T cells have been paradoxically linked to immunopathological responses in human cutaneous leishmaniasis. Transcriptome analysis of lesions from Leishmania braziliensis patients revealed that genes associated with the cytolytic pathway are highly expressed and CD8⁺ T cells from lesions exhibited a cytolytic phenotype. To determine if CD8⁺ T cells play a causal role in disease, we turned to a murine model. These studies revealed that disease progression and metastasis in L. braziliensis infected mice was independent of parasite burden and was instead directly associated with the presence of CD8⁺ T cells. In mice with severe pathology, we visualized CD8⁺ T cell degranulation and lysis of L. braziliensis infected cells. Finally, in contrast to wild-type CD8⁺ T cells, perforin-deficient cells failed to induce disease. Thus, we show for the first time that cytolytic CD8⁺ T cells mediate immunopathology and drive the development of metastatic lesions in cutaneous leishmaniasis.
Keywords in Portuguese
Leishmaniose CutâneaLeishmania braziliensis
Citotoxicidade imunológica
Linfócitos T Citotóxicos
Ratos
Keywords
Leishmaniasis, CutaneousLeishmania braziliensis
Cytotoxicity, Immunologic
T-Lymphocytes, Cytotoxic
Mice
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