Differential Dermal Expression of CCL17 and CCL18 in Tuberculoid and Lepromatous Leprosy

Autor: Glenna J. Peterson, Richard D. Wells, Susan J. F. van den Eeden, Chhatra B. Kunwar, James C. Vary, William R. Berrington, Thomas R. Hawn, Annemieke Geluk, Kapil D. Neupane, Deanna A. Hagge
Rok vydání: 2014
Předmět:
Male
Bacterial Diseases
Chemokine
Pathology
Erythema Nodosum
0302 clinical medicine
Medicine and Health Sciences
Cluster Analysis
CCL17
Mycobacterium leprae
Skin
Innate Immune System
0303 health sciences
Lepromatous leprosy
integumentary system
biology
medicine.diagnostic_test
lcsh:Public aspects of medicine
Middle Aged
Leprosy
Tuberculoid
Interleukin-10
3. Good health
Leprosy
Lepromatous
Infectious Diseases
Chemokines
CC
Female
Leprosy
Research Article
Neglected Tropical Diseases
Adult
medicine.medical_specialty
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
Immunology
Microbiology
Young Adult
03 medical and health sciences
Biopsy
medicine
Humans
030304 developmental biology
business.industry
Macrophages
Immunity
Public Health
Environmental and Occupational Health
CCL18
Biology and Life Sciences
lcsh:RA1-1270
Gene Expression Regulation
Bacterial
Tropical Diseases
medicine.disease
biology.organism_classification
Immune System
biology.protein
Chemokine CCL17
business
Biomarkers
030215 immunology
Zdroj: PLoS Neglected Tropical Diseases, Vol 8, Iss 11, p e3263 (2014)
PLoS Neglected Tropical Diseases, 8(11)
PLoS Neglected Tropical Diseases
ISSN: 1935-2735
DOI: 10.1371/journal.pntd.0003263
Popis: Background Leprosy is characterized by polar clinical, histologic and immunological presentations. Previous immunologic studies of leprosy polarity were limited by the repertoire of cytokines known at the time. Methodology We used a candidate gene approach to measure mRNA levels in skin biopsies from leprosy lesions. mRNA from 24 chemokines and cytokines, and 6 immune cell type markers were measured from 85 Nepalese leprosy subjects. Selected findings were confirmed with immunohistochemistry. Principal Results Expression of three soluble mediators (CCL18, CCL17 and IL-10) and one macrophage cell type marker (CD14) was significantly elevated in lepromatous (CCL18, IL-10 and CD14) or tuberculoid (CCL17) lesions. Higher CCL18 protein expression by immunohistochemistry and a trend in increased serum CCL18 in lepromatous lesions was observed. No cytokines were associated with erythema nodosum leprosum or Type I reversal reaction following multiple comparison correction. Hierarchical clustering suggested that CCL18 was correlated with cell markers CD209 and CD14, while neither CCL17 nor CCL18 were highly correlated with classical TH1 and TH2 cytokines. Conclusions Our findings suggest that CCL17 and CCL18 dermal expression is associated with leprosy polarity.
Author Summary Leprosy presents with a polarized spectrum, with lepromatous leprosy having high bacillary numbers and TH2 dermal cytokines, versus tuberculoid leprosy showing very few bacilli and TH1 cytokines. The mechanism underlying this polarized presentation is largely unknown. In the following study, we isolated mRNA from skin biopsies from 85 individuals with leprosy and measured the expression of a panel of 24 cytokines and 6 cell markers. We found that three soluble mediators (CCL17, CCL18 and IL10) and one cell marker (CD14) were differentially expressed in leprosy dermal lesions. CCL18 and IL10 were more highly expressed within lepromatous lesions, and CCL17 and CD14 were more highly expressed within tuberculoid lesions. In addition, CCL18 protein expression was confirmed by immunostaining. CCL17 and CCL18, were more strongly associated with leprosy polarity than traditional TH1 and TH2 cytokines. These data suggest that newer soluble chemokines may be important in leprosy pathogenesis and uncover a molecular signature of the two polar phenotypes of leprosy, which may be useful in future diagnostics.
Databáze: OpenAIRE
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