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International Immunology Advance Access published online on October 11, 2006
International Immunology, doi:10.1093/intimm/dxl097
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received July 13, 2005
Accepted September 5, 2006

Article

Differential induction of Th1-prone immunity by human dendritic cells activated with Sporothrix schenckii of cutaneous and visceral origins to determine their different virulence

Takeshi Uenotsuchi 1 *, Satoshi Takeuchi 1, Tetsuo Matsuda 1, Kazunori Urabe 1, Tetsuya Koga 1, Hiroshi Uchi 1, Takeshi Nakahara 1, Shuji Fukagawa 1, Masako Kawasaki 2, Hideko Kajiwara 3, Shin-ichi Yoshida 3, Yoichi Moroi 1, and Masutaka Furue 1

1 Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan
2 Department of Dermatology, Kanazawa Medical University, Ishikawa, Japan
3 Department of Bacteriology, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan

* To whom correspondence should be addressed.
Takeshi Uenotsuchi, E-mail: uenotti{at}dermatol.med.kyushu-u.ac.jp


  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 Th1 response, as evidenced by abundant IFN-{gamma} production, while the S. shenckii of visceral origins induced only minimal dendritic cell activation and Th1 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 Th1 response, other than immune status or the host, may be a factor for their different clinical manifestations.

Keywords: dendritic cells; Sporothrix schenckii; Th1.
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