title: Differential induction of Th1-prone immunity by human dendritic cells activated with Sporothrix schenckii of cutaneous and visceral origins to determine their different virulence.
abstract: Sporotrichosis is caused by a thermo-dependent dimorphic fungus, Sporothrix schenckii. The major clinical manifestations occur in the skin; however, cases of visceral manifestations have also been increasingly reported with some being observed in immune compromised patients. Different virulence of individual S. schenckii strain as well as immune status of the host could contribute to form such different clinical manifestations. Thus, the purpose of the study was to investigate whether different virulence of individual S. schenckii could be a factor for such clinical difference. We investigated the interactions between human monocyte-derived dendritic cells (MoDCs) and S. schenckii, assessed by (i) morphological features, (ii) surface marker expressions, cytokine productions, (iii) signaling pathways and (iv) allostimulatory activity of the activated MoDCs. Immature MoDCs, obtained from peripheral blood monocytes supplemented with granulocyte macrophage colony-stimulating factor and IL-4, were stimulated with S. schenckii strains of both yeasts and conidia forms of different origins (cutaneous isolates: KMU4649, IFM5906 and IFM46010; visceral isolates: KMU4648, IFM41598 and ATCC26331) to be used for various assays. Through the analysis, we found that the cutaneous S. shenckii of cutaneous origins were more potent to activate MoDCs to induce strong T(h)1 response, as evidenced by abundant IFN-gamma production, while the S. shenckii of visceral origins induced only minimal dendritic cell activation and T(h)1 induction. The p38 mitogen-activated protein kinase and c-Jun N-terminal kinase signaling pathways appeared to be associated with the differential activation of the MoDCs by S. schenckii of cutaneous and the visceral origins. Overall, we concluded that the differential activation of MoDCs by S. schenckii of cutaneous and visceral origins to induce T(h)1 response, other than immune status or the host, may be a factor for their different clinical manifestations.
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan. uenotti@dermatol.med.kyushu-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uenotsuchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Matsuda
authors.forename: Kazunori
authors.initials: K
authors.lastname: Urabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Koga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakahara
authors.forename: Shuji
authors.initials: S
authors.lastname: Fukagawa
authors.forename: Masako
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Hideko
authors.initials: H
authors.lastname: Kajiwara
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Moroi
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
mesh_terms: D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D003881:Dermatomycoses / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D013175:Sporothrix / Q000145:classification* / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D013174:Sporotrichosis / Q000382:microbiology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D014774:Virulence