Inkeles, MS;
Teles, RM;
Pouldar, D;
Andrade, PR;
Madigan, CA;
Lopez, D;
Ambrose, M;
... Modlin, RL; + view all
(2016)
Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy.
JCI Insight
, 1
(15)
, Article e88843. 10.1172/jci.insight.88843.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/jci.insight.88843 |
| Publisher version: | http://dx.doi.org/10.1172/jci.insight.88843 |
| Language: | English |
| Additional information: | Copyright © 2016, American Society for Clinical Investigation. This is an Open Access article. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1519842 |
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