TLR signaling fine-tunes anti-influenza B cell responses without regulating effector T cell responses
TLR signaling fine-tunes anti-influenza B cell responses without regulating effector T cell responses
复制标题
DOI：
10.4049/jimmunol.178.4.2182
复制
发表时间：
2007-02-15
影响因子：
4.4
通讯作者：
Marsland, Benjamin J.
中科院分区：
文献类型：
--
作者：
Heer, Alex K.;Shamshiev, Abdijapar;Marsland, Benjamin J.
流感是一种ssRNA病毒，其导致广泛的发病率和死亡率;然而，驱动体内适应性抗流感免疫应答的先天免疫机制尚未完全阐明。TLR是模式识别受体，其结合进化上保守的病原体相关分子模式，诱导树突状细胞成熟，并因此帮助有效免疫应答的发展。我们已经研究了TLR在驱动有效的T和B细胞对流感病毒的应答中的作用。我们发现TLR 3及其相关的衔接分子Toll/IL-R结构域的衔接诱导IFN-β在CD 4（+）或CD 8（+）T细胞对流感病毒的应答中不起作用，也不影响流感特异性B细胞应答。令人惊讶的是，TLR 7和MyD 88在流感病毒感染后的T细胞活化和效应子功能中也发挥了可忽略的作用;然而，它们的信号传导对于调节抗流感B细胞Ab同种型转换至关重要。适当的抗流感不道德反应的诱导涉及直接刺激B细胞上的TLR和TLR诱导的IFN-α的产生，其起到减少IgG 1和增加IgG 2a/c类别转换的作用。值得注意的是，通过CD 40-CD 40 L相互作用在B细胞或T细胞上的直接TLR信号传导足以支持B细胞增殖和IgG 1产生，而IFN-α对于微调同种型转换的性质至关重要。总之，这些数据揭示TLR信号传导不是抗流感T细胞应答所需的，而是通过直接和间接手段协调适当的抗流感B细胞应答。免疫学杂志，2007，178：2182-2191.
Influenza is a ssRNA virus that has been responsible for widespread morbidity and mortality; however, the innate immunological mechanisms that drive the adaptive anti-influenza immune response in vivo are yet to be fully elucidated. TLRs are pattern recognition receptors that bind evolutionarily conserved pathogen-associated molecular patterns, induce dendritic cell maturation, and consequently aid the development of effective immune responses. We have examined the role of TLRs in driving effective T and B cell responses against influenza virus. We found TLR3 and its associated adapter molecule, Toll/IL-R domain-containing adaptor-inducing IFN-beta, did not play a role in the development of CD4(+) or CD8(+) T cell responses against influenza virus, nor did they influence influenza-specific B cell responses. Surprisingly, TLR7 and MyD88 also played negligible roles in T cell activation and effector function upon infection with influenza virus; however, their signaling was critical for regulating anti-influenza B cell Ab isotype switching. The induction of appropriate anti-influenza Immoral responses involved stimulation of TLRs on B cells directly and TLR-induced production of IFN-alpha, which acted to reduce IgG1 and increase IgG2a/c class switching. Notably, direct TLR signaling on B cells or T cell help through the CD40-CD40L interaction was sufficient to support B cell proliferation and IgG1 production, whereas IFN-alpha was critical for fine-tuning the nature of the isotype switch. Taken together, these data reveal that TLR signaling is not required for anti-influenza T cell responses, but through both direct and indirect means orchestrates appropriate anti-influenza B cell responses. The Journal of Immunology, 2007, 178: 2182-2191.