Uchida Takefumi, Scumpia Philip O, Murasko Donna M, Seki Shuhji, Woulfe Susan, Clare-Salzler Michael J, Moldawer Lyle L
Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Road, Gainesville, FL 32610, USA.
J Immunol. 2007 Mar 15;178(6):3886-92. doi: 10.4049/jimmunol.178.6.3886.
TLRs initiate the host immune response to microbial pathogens by activating cells of the innate immune system. Dendritic cells (DCs) can be categorized into two major groups, conventional DCs (including CD8(+) and CD8(-) DCs) and plasmacytoid DCs. In mice, these subsets of DCs express a variety of TLRs, with conventional DCs responding in vitro to predominantly TLR3, TLR4, TLR5, and TLR9 ligands, and plasmacytoid DCs responding mainly to TLR7 and TLR9 ligands. However, the in vivo requirement of DCs to initiate immune responses to specific TLR agonists is not fully known. Using mice depleted of >90% of CD11c(+) MHC class II(+) DCs, we demonstrate that cellular recruitment, including CD4(+) T cell and CX5(+)DX5(+) NK cell recruitment to draining lymph nodes following the footpad administration of TLR4 and TLR5 agonists, is dramatically decreased upon reduction of DC numbers, but type I IFN production can partially substitute for DCs in response to TLR3 and TLR7 agonists. Interestingly, TLR ligands can activate T cells and NK cells in the draining lymph nodes, even with reduced DC numbers. The findings reveal considerable plasticity in the response to TLR agonists, with TLR4 and TLR5 agonists sharing the requirement of DCs for subsequent lymph node recruitment of NK and T cells.
Toll样受体（TLRs）通过激活固有免疫系统的细胞来启动宿主对微生物病原体的免疫反应。树突状细胞（DCs）可分为两大类，即传统DCs（包括CD8(+)和CD8(-) DCs）和浆细胞样DCs。在小鼠中，这些DCs亚群表达多种TLRs，传统DCs在体外主要对TLR3、TLR4、TLR5和TLR9配体产生反应，而浆细胞样DCs主要对TLR7和TLR9配体产生反应。然而，DCs在体内启动对特定TLR激动剂免疫反应的需求尚不完全清楚。利用CD11c(+) MHC II类(+) DCs缺失>90%的小鼠，我们证明，在足垫注射TLR4和TLR5激动剂后，包括CD4(+) T细胞和CX5(+)DX5(+) NK细胞募集至引流淋巴结的细胞募集，在DC数量减少时显著降低，但I型干扰素的产生在对TLR3和TLR7激动剂的反应中可部分替代DCs。有趣的是，即使DC数量减少，TLR配体仍可激活引流淋巴结中的T细胞和NK细胞。这些发现揭示了对TLR激动剂反应具有相当大的可塑性，TLR4和TLR5激动剂在随后NK和T细胞向淋巴结募集中都需要DCs。
