Role of TLR4 in allergic sensitization to food proteins in mice
Role of TLR4 in allergic sensitization to food proteins in mice
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DOI：
10.1111/j.1398-9995.2006.01012.x
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发表时间：
2006-01-01
期刊：
影响因子：
12.4
通讯作者：
Sampson, HA
中科院分区：
文献类型：
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作者：
Berin, MC;Zheng, Y;Sampson, HA
对食物蛋白质和其他过敏原的过敏性致敏正在增加。这种增加的一种假设是，感染率降低或暴露于微生物产品使免疫系统容易因缺乏调节细胞的发育而对无害抗原产生不适当的反应。我们假设组成型Toll样受体（TLR）4信号（可能通过水生植物群）可以抑制食物蛋白过敏性致敏的发展。我们通过使两种遗传背景（C3 H和BALB/c）的TLR 4+和TLR 4-小鼠对两种常见食物过敏原[β-乳球蛋白（β LG）和花生（PN）]敏感来验证这一假设。B细胞反应不受TLR 4状态的显著影响。与TLR 4充足的C3 H小鼠相比，TLR 4缺陷的C3 H小鼠中的T细胞应答是Th 2偏斜的，但在BALB/c背景下的TLR 4缺陷小鼠中未观察到这种Th 2偏斜模式。在过敏敏感的C3 H小鼠中，TLR 4缺乏与PN过敏反应的严重程度增加相关，而β LG过敏反应的严重程度降低。在过敏抵抗的BALB/c小鼠中，TLR 4缺乏不足以使小鼠对PN诱导的过敏反应敏感。我们的结论是，虽然TLR 4的状态可以影响T细胞反应和过敏反应的严重程度，影响的性质是高度抗原和应变依赖性。
Allergic sensitization to food proteins and other allergens is increasing in prevalence. One hypothesis for this increase is that the decreased rate of infections or exposure to microbial products leaves the immune system susceptible to inappropriate reactivity to innocuous antigens through the lack of development of regulatory cells. We hypothesized that constitutive Toll-like receptor (TLR)4 signaling (presumably via the commensal flora) could inhibit the development of allergic sensitization to food proteins. We tested this hypothesis by sensitizing TLR4+ and TLR4- mice on two genetic backgrounds, C3H and BALB/c, to two common food allergens [beta-lactoglobulin (beta LG) and peanut (PN)]. B-cell responses were not significantly influenced by TLR4 status. T-cell responses were Th2 skewed in TLR4-deficient C3H mice compared with TLR4 sufficient C3H mice, but this pattern of Th2 skewing was not observed in TLR4-deficient mice on a BALB/c background. In anaphylaxis-susceptible C3H mice, TLR4 deficiency was associated with increased severity of anaphylaxis to PN, and decreased severity of anaphylaxis to beta LG. In anaphylaxis-resistant BALB/c mice, TLR4 deficiency was not sufficient to render mice susceptible to PN-induced anaphylaxis. We conclude that although TLR4 status can influence T-cell responses and anaphylaxis severity, the nature of the influence is highly antigen- and strain-dependent.