TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes
TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes
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DOI：
10.4049/jimmunol.1403173
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发表时间：
2015-08-01
影响因子：
4.4
通讯作者：
Dalpke, Alexander H.
中科院分区：
文献类型：
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作者：
Eigenbrod, Tatjana;Pelka, Karin;Dalpke, Alexander H.
微生物核酸是一类重要的病原体相关分子模式（PAMP），能有效地激活先天免疫。在小鼠中，TLR 13最近被鉴定为检测细菌23 S rRNA内的高度保守区域。然而，TLR 13在人类中不表达，其人类同源物的身份仍然难以捉摸。此外，细菌RNA对诱导针对整个细菌的先天免疫应答的贡献仍然没有充分确定。在目前的研究中，我们表明，人单核细胞响应细菌RNA分泌IL-6，TNF和IFN-β，这是严重依赖于溶酶体成熟。使用小干扰RNA和过表达，我们明确地确定TLR 8作为受体的细菌RNA在原代人单核细胞衍生的巨噬细胞。我们进一步证明了TLR 8所感知的序列基序与TLR 13所识别的序列基序明显不同。此外，TLR 8依赖的细菌RNA检测是触发单核细胞激活的化脓性链球菌感染的关键。链球菌内的细菌RNA也是小鼠免疫细胞的主要刺激物，凸显了RNA传感在防御感染方面的生理相关性。
Microbial nucleic acids constitute an important group of pathogen-associated molecular patterns (PAMPs) that efficiently trigger innate immune activation. In mice, TLR13 has recently been identified to sense a highly conserved region within bacterial 23S rRNA. However, TLR13 is not expressed in humans, and the identity of its human homolog remains elusive. Moreover, the contribution of bacterial RNA to the induction of innate immune responses against entire bacteria is still insufficiently defined. In the current study, we show that human monocytes respond to bacterial RNA with secretion of IL-6, TNF, and IFN-beta, which is critically dependent on lysosomal maturation. Using small interfering RNA and overexpression, we unambiguously identify TLR8 as receptor for bacterial RNA in primary human monocyte-derived macrophages. We further demonstrate that the sequence motif sensed by TLR8 is clearly distinct from that recognized by TLR13. Moreover, TLR8-dependent detection of bacterial RNA was critical for triggering monocyte activation in response to infection with Streptococcus pyogenes. Bacterial RNA within streptococci was also a dominant stimulus for murine immune cells, highlighting the physiological relevance of RNA sensing in defense of infections.