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J Invest Dermatol. 2015 Jan;135(1):94-101. doi: 10.1038/jid.2014.305. Epub 2014 Jul 18.

Genomic profiling of human Leishmania braziliensis lesions identifies transcriptional modules associated with cutaneous immunopathology.

Author information

1
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
2
Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais-INCT-DT(CNPq/MCT), Serviço de Imunologia, Hospital Universitario Prof. Edgard Santos, Universidade Federal da Bahia Salvador, Bahia, Brazil.
3
Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
4
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: pscott@vet.upenn.edu.
5
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: beiting@vet.upenn.edu.

Abstract

The host immune response has a critical role not only in protection from human leishmaniasis but also in promoting disease severity. Although candidate gene approaches in mouse models of leishmaniasis have been extremely informative, a global understanding of the immune pathways active in lesions from human patients is lacking. To address this issue, genome-wide transcriptional profiling of Leishmania braziliensis-infected cutaneous lesions and normal skin controls was carried out. A signature of the L. braziliensis skin lesion was defined, which includes over 2,000 differentially regulated genes. Pathway-level analysis of this transcriptional response revealed key biological pathways present in cutaneous lesions, generating a testable 'metapathway' model of immunopathology and providing new insights for treatment of human leishmaniasis.

PMID:
25036052
PMCID:
PMC4268311
DOI:
10.1038/jid.2014.305
[Indexed for MEDLINE]
Free PMC Article

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