title: Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy.
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 withMMP12as 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.
authors.affiliation: Department of Molecular, Cell, and Developmental Biology and.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Inkeles
authors.affiliation: Division of Dermatology, David Geffen School of Medicine at UCLA, California, USA.
authors.forename: Rosane Mb
authors.initials: RM
authors.lastname: Teles
authors.affiliation: Division of Dermatology, David Geffen School of Medicine at UCLA, California, USA.
authors.forename: Delila
authors.initials: D
authors.lastname: Pouldar
authors.affiliation: Division of Dermatology, David Geffen School of Medicine at UCLA, California, USA.
authors.forename: Priscila R
authors.initials: PR
authors.lastname: Andrade
authors.affiliation: Division of Dermatology, David Geffen School of Medicine at UCLA, California, USA.
authors.forename: Cressida A
authors.initials: CA
authors.lastname: Madigan
authors.affiliation: Department of Molecular, Cell, and Developmental Biology and.
authors.forename: David
authors.initials: D
authors.lastname: Lopez
authors.affiliation: Department of Molecular, Cell, and Developmental Biology and.
authors.forename: Mike
authors.initials: M
authors.lastname: Ambrose
authors.affiliation: Division of Infection and Immunity, University College London, London, United Kingdom.
authors.forename: Mahdad
authors.initials: M
authors.lastname: Noursadeghi
authors.affiliation: Leprosy Laboratory, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Euzenir N
authors.initials: EN
authors.lastname: Sarno
authors.affiliation: Department of Dermatology, University of Southern California School of Medicine, Los Angeles, California, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Rea
authors.affiliation: Department of Dermatology, University of Southern California School of Medicine, Los Angeles, California, USA.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Ochoa
authors.affiliation: Department of Molecular, Cell, and Developmental Biology and.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Iruela-Arispe
authors.affiliation: Department of Dermatology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Swindell
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Tom Hm
authors.initials: TH
authors.lastname: Ottenhoff
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Geluk
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Bloom
authors.affiliation: Department of Molecular, Cell, and Developmental Biology and.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Division of Dermatology, David Geffen School of Medicine at UCLA, California, USA.|Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
mesh_terms: D000293:Adolescent; D000328:Adult; D004893:Erythema Nodosum / Q000235:genetics / Q000276:immunology; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D007918:Leprosy / Q000235:genetics* / Q000276:immunology*; D015440:Leprosy, Lepromatous / Q000235:genetics / Q000276:immunology; D015441:Leprosy, Tuberculoid / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D059467:Transcriptome; D055815:Young Adult