Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 208, Issue 5, Pages 885-891Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20102318
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Funding
- University of Mainz
- Deutsche Forschungsgemeinschaft (DFG) [SFB548]
- DFG-NWO (The Netherlands Organization for Scientific Research) [DN 93-525, Ste 833/6-1]
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Migratory skin dendritic cells (DCs) are thought to play an important role in priming T cell immune responses against Leishmania major, but DC subtypes responsible for the induction of protective immunity against this pathogen are still controversial. In this study, we analyzed the role of Langerin(+) skin-derived DCs in the Leishmania model using inducible in vivo cell ablation. After physiologically relevant low-dose infection with L. major (1,000 parasites), mice depleted of all Langerin(+) DCs developed significantly smaller ear lesions with decreased parasite loads and a reduced number of CD4(+) Foxp3(+) regulatory T cells (T reg cells) as compared with controls. This was accompanied by increased interferon gamma production in lymph nodes in the absence of Langerin(+) DCs. Moreover, selective depletion of Langerhans cells (LCs) demonstrated that the absence of LCs, and not Langerin(+) dermal DC, was responsible for the reduced T reg cell immigration and the enhanced Th1 response, resulting in attenuated disease. Our data reveal a unique and novel suppressive role for epidermal LCs in L. major infection by driving the expansion of T reg cells. A better understanding of the various roles of different DC subsets in cutaneous leishmaniasis will improve the development of a potent therapeutic/prophylactic vaccine.
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