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.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.