A role for TLR signaling during B cell activation in antiretroviral-treated HIV individuals.
A role for TLR signaling during B cell activation in antiretroviral-treated HIV individuals.
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TLR 信号传导在接受抗逆转录病毒治疗的 HIV 个体 B 细胞激活过程中的作用。
DOI：
10.1089/aid.2013.0115
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发表时间：
2013
影响因子：
1.5
通讯作者：
Landay,Alan
中科院分区：
文献类型：
--
作者：
Siewe,Basile;Keshavarzian,Ali;French,Audrey;Demarais,Patricia;Landay,Alan
抗逆转录病毒治疗（ART）期间持续存在的B细胞活化的潜在机制尚不清楚。Toll样受体（TLR）信号传导是先天性细胞活化的关键介质，尽管B细胞表达TLR，但很少有研究调查TLR信号传导在HIV感染期间B细胞活化中的作用。我们通过评估ART治疗的HIV感染受试者（HIVART+）的B细胞的活化表型和TLR表达/反应性来解决这个问题。我们评估了HIV发病过程中涉及B细胞介导的T细胞转感染的活化标志物。我们发现HIVART+和HIV-受试者的B细胞之间TLR表达没有显著差异。然而，HIVART+受试者的B细胞表现出IL-6（p=0.0051）、T细胞同源配体CD 40（p=0.0475）、CD 54（p=0.0229）和磷酸化p38（p<0.0001）（TLR信号传导的标志物）的内源性表达水平升高。在体外，与HIV-受试者的B细胞相比，HIVART+受试者的B细胞对TLR刺激的反应较低。HIV−受试者体内TLR刺激的B细胞的活化表型与HIVART+个体的体外B细胞相似。TLR 2刺激是B细胞活化的有效介质，而B细胞对TLR 4刺激的反应最小。与HIV−受试者相比，HIVART+受试者的血清脂磷壁酸（TLR 2配体）水平显著较高（p=0.0207），与病毒载量呈正相关（p= 0.0127，r =0.6453）。我们的数据表明，在HIV感染过程中，TLR激活的B细胞可能发挥致病作用，并且来自HIVART+受试者的B细胞对体外TLR刺激有反应，但表现出TLR耐受表型，这表明先前体内TLR刺激。
The mechanisms underlying B cell activation that persists during antiretroviral therapy (ART) are unknown. Toll-like receptor (TLR) signaling is a critical mediator of innate cell activation and though B cells express TLRs, few studies have investigated a role for TLR signaling in B cell activation during HIV infection. We addressed this question by assessing the activated phenotype and TLR expression/responsiveness of B cells from ART-treated HIV-infected subjects (HIVART+). We evaluated activation markers implicated in B cell-mediated T celltransinfection during HIV pathogenesis. We found no significant difference in TLR expression between B cells of HIVART+and HIV−subjects. However, B cells of HIVART+subjects exhibited heightened endogenous expression levels of IL-6 (p=0.0051), T cell cognate ligands CD40 (p=0.0475), CD54 (p=0.0229), and phosphorylated p38 (p<0.0001), a marker of TLR signaling.In vitro,B cells of HIVART+individuals were less responsive to TLR stimulation compared to B cells of HIV−subjects. The activated phenotype ofin vitroTLR-stimulated B cells of HIV−subjects was similar toex vivoB cells from HIVART+individuals. TLR2 stimulation was a potent mediator of B cell activation, whereas B cells were least responsive to TLR4 stimulation. Compared to HIV−subjects, the serum level of lipoteichoic acid (TLR2 ligand) in HIVART+subjects was significantly higher (p=0.0207), correlating positively with viral load (p=0.0127,r=0.6453). Our data suggest that during HIV infection TLR-activated B cells may exert a pathogenic role and B cells from HIVART+subjects respond toin vitroTLR stimulation, yet exhibit a TLR tolerant phenotype suggesting priorin vivoTLR stimulation.
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DOI：
10.1086/597476
发表时间：
2009-04-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Jiang W;Lederman MM;Hunt P;Sieg SF;Haley K;Rodriguez B;Landay A;Martin J;Sinclair E;Asher AI;Deeks SG;Douek DC;Brenchley JM
通讯作者：
Brenchley JM
影响因子：
3.6
作者：
Smith, Thomas J.;Yamamoto, Kouhei;Kitagawa, Masanobu
通讯作者：
Kitagawa, Masanobu
影响因子：
3.8
作者：
POULIN, L;PAQUETTE, N;DARVEAU, A
通讯作者：
DARVEAU, A
影响因子：
32.4
作者：
Doyle, SE;Vaidya, SA;Cheng, G
通讯作者：
Cheng, G
正常人和 HIV 感染者 B 细胞产生淋巴因子
影响因子：
5.2
作者：
J. Kehrl;P. Rieckmann;E. Kozlow;A. Fauci
通讯作者：
A. Fauci