Use of Genetic Profiling in Leprosy to Discriminate Clinical Forms of the Disease

Author:

Bleharski Joshua R.12345,Li Huiying12345,Meinken Christoph12345,Graeber Thomas G.12345,Ochoa Maria-Teresa12345,Yamamura Masahiro12345,Burdick Anne12345,Sarno Euzenir N.12345,Wagner Manfred12345,Röllinghoff Martin12345,Rea Thomas H.12345,Colonna Marco12345,Stenger Steffen12345,Bloom Barry R.12345,Eisenberg David12345,Modlin Robert L.12345

Affiliation:

1. Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.

2. Division of Dermatology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.

3. Department of Chemistry and Biochemistry and Department of Biological Chemistry, Howard Hughes Medical Institute, UCLA–Department of Energy Institute of Genomics and Proteomics, UCLA, Los Angeles, CA 90095, USA.

4. Institut für Klinische Mikrobiologie, Immunologie, und Hygiene, Universität Erlangen, 91054 Erlangen, Germany.

5. Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.

Abstract

Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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