Fakher et al. recently reported (1) that DNA from Leishmania major parasites activated mouse myeloid dendritic cells (mDC) and plasmacytoid DC (pDCs) in a TLR 9-dependent manner and that L. major-infected TLR9−/− mice expressed increased levels of IL-4 and developed an aggravated infection compared with controls. Whereas all these observations confirm our previous results (2, 3), two sets of data are in conflict with our findings.
First, unlike in our study (2), there was a 2.5-fold decrease of IFN-γ mRNA in the lymph nodes of L. major-infected TLR9−/− mice (1). Two additional results (TLR9-dependent IFN-γ production in vitro using mDCs, OVA, and transgenic OT-II CD4+ T cells and partial TLR9 dependency of the IFN-γ production by splenic CD4+ T cells after an i.v. L. major infection) led the authors to postulate that TLR9 signaling in DCs is necessary for IFN-γ production by CD4+ T cells. However, the heterologous in vitro system essentially tests the adjuvanticity of TLR9 and the i.v. infection does not imitate cutaneous leishmaniasis. When we analyzed the expression of the IFN-γ protein by lymph node CD4+ T cells from cutaneously infected mice, we observed no difference between TLR9−/− and control mice (2). Thus, the TLR9-dependent cytokine production of mDCs does not impair Th1 development in vivo. If that were the case, TLR9−/− mice would fail to control L. major infection.
Second, Fakher et al. report that their pDCs responded to LPS (1). Because pDCs do not express TLR4 (4), contamination of their pDC preparation (purity 85%) with mDCs is likely to account for the LPS responsiveness.
- Copyright © 2009 by The American Association of Immunologists, Inc.
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