title: Local activation of the innate immune system in Buruli ulcer lesions.
abstract: Buruli ulcer (BU) caused by Mycobacterium ulcerans is a chronic necrotizing disease of the skin and the underlying soft tissue. Fat tissue necrosis accompanied by minimal inflammation is considered the most reliable histopathologic feature of BU. There may be a constant influx of inflammatory cells to the sites of active infection but these are thought to be killed by mycolactone, a polyketide toxin produced by M. ulcerans, through apoptosis and necrosis. Here we describe the spatial correlations between mycobacterial load and the expression of dendritic cell (DC) surface markers (cluster of differentiation (CD)83, CD11c, and CD123), the Toll-like receptor (TLR) 9 and pro- and anti-inflammatory cytokines (IL-8, IL-6, tumor necrosis factor-alpha (TNF-alpha), IFN-alpha, IL-12p40, IL-10, and IFN-gamma) within BU lesions. Although IL-8, IL-6, and TNF-alpha messenger RNA (mRNA) was detectable by real-time PCR in all lesions, the expression of the other cytokines was only found as small foci in some lesions. Correlations of the distribution of mRNA encoding the activation marker CD83 and the DC subset markers CD123 and CD11c indicate that both activated plasmacytoid and myeloid dendritic cells were present in the lesions. Results suggest that M. ulcerans specific immune responses may develop once therapeutic interventions have limited the production of mycolactone.
authors.affiliation: Swiss Tropical Institute, Department of Medical Parasitology and Molecular Immunology, Basel, Switzerland.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Peduzzi
authors.forename: Célia
authors.initials: C
authors.lastname: Groeper
authors.forename: Daniela
authors.initials: D
authors.lastname: Schütte
authors.forename: Paul
authors.initials: P
authors.lastname: Zajac
authors.forename: Simona
authors.initials: S
authors.lastname: Rondini
authors.forename: Ernestina
authors.initials: E
authors.lastname: Mensah-Quainoo
authors.forename: Giulio Cesare
authors.initials: GC
authors.lastname: Spagnoli
authors.forename: Gerd
authors.initials: G
authors.lastname: Pluschke
authors.forename: Claudia Andrea
authors.initials: CA
authors.lastname: Daubenberger
mesh_terms: D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation; D019911:Mycobacterium ulcerans / Q000378:metabolism*; D009336:Necrosis; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D017192:Skin Diseases, Bacterial / Q000276:immunology*; D012883:Skin Ulcer / Q000276:immunology* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha