Requirement for TLR9 in the immunomodulatory activity of Propionibacterium acnes
Requirement for TLR9 in the immunomodulatory activity of Propionibacterium acnes
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DOI：
10.4049/jimmunol.174.7.4295
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Freudenberg, MA
中科院分区：
文献类型：
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作者：
Kalis, C;Gumenscheimer, M;Freudenberg, MA
痤疮丙酸杆菌(前身为细小棒状杆菌)是人类菌群的一部分，因此与多种人类疾病有关。它具有很强的免疫调节活性，这使该细菌在预防和治疗性疫苗接种方面具有重要意义。参与诱导这些活性的细菌成分(S)和宿主受体(S)知之甚少。在这项研究中，我们表明TLR9在脾内引发灭活痤疮杆菌的特有效应中起关键作用，如髓外造血和器官增大，以及肝脏肉芽肿的形成。此外，对脂多糖、脂类A、合成脂肽Pam(3)、CysK(4)或完全灭活的细菌的反应，能够过度产生肿瘤坏死因子-α和干扰素-γ的能力存在于痤疮假单胞菌诱导的野生型小鼠中，而不是TLR9(-/-)小鼠。最后，痤疮假单胞菌接种未能诱导TLR9(-/-)小鼠对小鼠伤寒的抵抗力增强。因此，TLR9在痤疮假单胞菌诱导免疫调节作用中起重要作用。由于干扰素-γ是这些作用的关键介质，而痤疮假单胞菌诱导的TLR9(-/-)小鼠的脾和肝脏中没有增强的干扰素-γ的表达，因此我们认为TLR9是痤疮假单胞菌诱导干扰素-γ所必需的。
Propionibacterium acnes (formerly Corynebactetium parvuin) is part of the human flora and, as such, is associated with several human pathologies. It possesses strong immunomodulatory activities, which makes this bacterium interesting for prophylactic and therapeutic vaccination. The bacterial component(s) and the host receptor(s) involved in the induction of these activities are poorly understood. We show in this study that TLR9 is crucial in generating the characteristic effects of killed P. acnes priming in the spleen, such as extramedullary hemopoiesis and organ enlargement, and granuloma formation in the liver. Furthermore, the ability to overproduce TNF-alpha and IFN-gamma in response to LPS, lipid A, synthetic lipopeptide Pam(3)CysK(4), or whole killed bacteria was present in P. acnes-primed wild-type, but not TLR9(-/-), mice. Finally, P. acnes priming failed to induce enhanced resistance to murine typhoid fever in TLR9(-/-) mice. Thus, TLR9 plays an essential role in the induction of immunomodulatory effects by P. acnes. Because IFN-gamma is a key mediator of these effects, and enhanced IFN-gamma mRNA expression was absent in spleen and liver of P. acnes-primed TLR9(-/-) mice, we conclude that TLR9 is required for the induction of IFN-gamma by P. acnes.