TLR4 on follicular dendritic cells: An activation pathway that promotes accessory activity

被引:39
|
作者
El Shikh, Motley Eldin M.
El Sayed, Rania M.
Wu, Yongzhong
Szakal, Andras K.
Tew, John G.
机构
[1] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA
[2] Virginia Commonwealth Univ, Anat & Neurobiol & Immunol Grp, Richmond, VA 23298 USA
来源
JOURNAL OF IMMUNOLOGY | 2007年 / 179卷 / 07期
关键词
D O I
10.4049/jimmunol.179.7.4444
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Microbial molecular patterns engage TLRs and activate dendritic cells and other accessory cells. Follicular dendritic cells (FDCs) exist in resting and activated states, but are activated in germinal centers, where they provide accessory function. We reasoned that FDCs might express TLRs and that engagement might activate FDCs by up-regulating molecules important for accessory activity. To test this hypothesis, TLR4 expression on FDCs was studied in situ with immunohistochemistry, followed by flow cytometry and RT-PCR analysis. TLR4 was expressed on FDC reticula in situ, and flow cytometry indicated that TLR4 was expressed on surface membranes and TLR4 message was readily apparent in FDCs by RT-PCR. Injecting mice or treating purified FDCs with LPS up-regulated molecules important for accessory activity including, FDC-Fc gamma RIIB, FDC-ICAM-1, and FDC-VCAM-1. Treatment of purified FDCs with LPS also induced intracellular phospho-I kappa B-alpha, indicating NF-kappa B activation, and that correlated with increased Fc gamma RIIB, ICAM-1, and VCAM-1. FDCs in C3H/HeJ mice were not activated with LPS even when mice were reconstituted with C3H/HeN leukocytes, suggesting that engagement of FDC-TLR4 is necessary for activation. Moreover, activated FDCs exhibited increased accessory activity in anti-OVA recall responses in vitro, and the FDC number could be reduced 4-fold if they were activated. In short, we report expression of TLR4 on FDCs for the first time and that engagement of FDC-TLR4 activated NF-kappa B, up-regulated expression of molecules important in FDC accessory function, including Fc gamma RIIB, ICAM-1, and VCAM-1, as well as FDC accessory activity in promoting recall IgG responses.
引用
收藏
页码:4444 / 4450
页数:7
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