Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy

David Geffen School of Medicine at UCLA. Department of Molecular. Cell, and Developmental Biology. California, USA.
David Geffen School of Medicine at UCLA. Division of Dermatology. California, USA.
David Geffen School of Medicine at UCLA. Division of Dermatology. California, USA.
David Geffen School of Medicine at UCLA. Division of Dermatology. California, USA.
David Geffen School of Medicine at UCLA. Division of Dermatology. California, USA.
David Geffen School of Medicine at UCLA. Department of Molecular. Cell, and Developmental Biology. California, USA.
David Geffen School of Medicine at UCLA. Department of Molecular. Cell, and Developmental Biology. California, USA.
University College London. Division of Infection and Immunity. London, United Kingdom.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
University of Southern California School of Medicine. Department of Dermatology. Los Angeles, CA, USA.
University of Southern California School of Medicine. Department of Dermatology. Los Angeles, CA, USA.
David Geffen School of Medicine at UCLA. Department of Molecular. Cell, and Developmental Biology. California, USA.
University of Michigan School of Medicine. Department of Dermatology. Ann Arbor, Michigan, USA.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands.
Harvard School of Public Health. Boston, Massachusetts, USA.
David Geffen School of Medicine at UCLA. Department of Molecular. Cell, and Developmental Biology. California, USA.
David Geffen School of Medicine at UCLA. Division of Dermatology. California, USA / UCLA. Department of Microbiology, Immunology and Molecular Genetics. Los Angeles, California, USA

Resumo em Inglês

Transcriptome profiles derived from the site of human disease have led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum, which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene coexpression modules by cell-type deconvolution. In lesions from tuberculoid leprosy patients, those with the self-limited form of the disease, dendritic cells were linked with MMP12 as part of a tissue remodeling network that contributes to granuloma formation. In lesions from lepromatous leprosy patients, those with disseminated disease, macrophages were linked with a gene network that programs phagocytosis. In erythema nodosum leprosum, neutrophil and endothelial cell gene networks were identified as part of the vasculitis that results in tissue injury. The present integrated computational approach provides a systems approach toward identifying cell-defined functional networks that contribute to host defense and immunopathology at the site of human infectious disease.

Palavras-chave

Hanseníase
Deconvolução de tipo celular
Vias imunológicas
Redes genéticas
Defesas do hospedeiro

Palavras-chave em inglês

Leprosy
immune pathways
Cell-type deconvolution
host defense
immune pathways
gene networks

Editor

American Society for Clinical Investigation

Referência

INKELES, Megan S. et al. Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy. JCI Insight, v.1, n.15, e88843, 16p, sept. 2016.

DOI

10.1172/jci.insight.88843

ISSN

2379-3708

Use este identificador para citar ou linkar para este item: https://www.arca.fiocruz.br/handle/icict/17861

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Direito Autoral

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