Use of genetic profiling in leprosy to discriminate clinical forms of the disease.
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.
Bleharski
Joshua R
JR
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Li
Huiying
H
Meinken
Christoph
C
Graeber
Thomas G
TG
Ochoa
Maria-Teresa
MT
Yamamura
Masahiro
M
Burdick
Anne
A
Sarno
Euzenir N
EN
Wagner
Manfred
M
Röllinghoff
Martin
M
Rea
Thomas H
TH
Colonna
Marco
M
Stenger
Steffen
S
Bloom
Barry R
BR
Eisenberg
David
D
Modlin
Robert L
RL
D000465:Algorithms; D016000:Cluster Analysis; D015169:Colony Count, Microbial; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D015440:Leprosy, Lepromatous / Q000145:classification* / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D015441:Leprosy, Tuberculoid / Q000145:classification* / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D025341:Principal Component Analysis; D011956:Receptors, Cell Surface / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors; D015854:Up-Regulation
D016207:Cytokines; C105298:LILRA2 protein, human; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors