Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany.
Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.
Front Cell Infect Microbiol. 2021 Mar 4;11:627630. doi: 10.3389/fcimb.2021.627630. eCollection 2021.
is a tick-transmitted obligate intracellular Gram-negative bacterium that replicates in neutrophils. It elicits febrile disease in humans and in animals. In a mouse model, elimination of required CD4 T cells, but was independent of IFN-γ and other classical antibacterial effector mechanisms. Further, mice deficient for immune recognition and signaling Toll-like receptor (TLR) 2, TLR4 or MyD88 were unimpaired in pathogen control. In contrast, animals lacking adaptor molecules of Nod-like receptors (NLR) such as RIP2 or ASC showed delayed clearance of . In the present study, we investigated the contribution of further pattern recognition receptor (PRR) pathways to the control of . Mice deficient for the NLR NOD2 had elevated bacterial loads in the early phase of infection, but were unimpaired in pathogen elimination. In contrast, animals lacking adaptor proteins of different C-type lectin receptors (CLR) such as DAP12, Fc-receptor γ-chain (FcRγ) and SYK controlled as efficiently as wild-type mice. Further, we investigated which PRR pathways are involved in the sensing of by generated Hoxb8 murine neutrophils. , recognition of by murine neutrophils was dependent on TLR- and MyD88 signaling. However, it remained intact in the absence of the NLR NOD1, NOD2 and NALP3 and of the CLR adaptor molecules DAP12 and FcRγ. From these results, we conclude that TLR rather than NLR or CLR are critical for the detection of by neutrophils although defective TLR-signaling is compensated probably because of the redundancy of the immune system.
是一种蜱传的专性细胞内革兰氏阴性菌，在中性粒细胞中复制。它在人类和动物中引起发热性疾病。在小鼠模型中， 消除需要 CD4 T 细胞，但与 IFN-γ 和其他经典的抗菌效应机制无关。此外，缺乏免疫识别和信号转导 Toll 样受体 (TLR) 2、TLR4 或 MyD88 的小鼠在病原体控制方面没有受损。相比之下，缺乏 Nod 样受体 (NLR) 衔接分子如 RIP2 或 ASC 的动物清除 速度较慢。在本研究中，我们研究了进一步的模式识别受体 (PRR) 途径对 控制的贡献。缺乏 NLR NOD2 的小鼠在感染早期的细菌负荷增加，但在病原体消除方面没有受损。相比之下，缺乏不同 C 型凝集素受体 (CLR) 的衔接蛋白的动物，如 DAP12、Fc 受体 γ 链 (FcRγ) 和 SYK，对 控制的效果与野生型小鼠一样有效。此外，我们研究了哪些 PRR 途径参与了 Hoxb8 小鼠中性粒细胞产生的 识别。 识别依赖于 TLR 和 MyD88 信号转导。然而，在缺乏 NLR NOD1、NOD2 和 NALP3 以及 CLR 衔接分子 DAP12 和 FcRγ 的情况下，它仍然完整。从这些结果中，我们得出结论，尽管 TLR 信号转导缺陷可能是由于免疫系统的冗余性而得到补偿，但 TLR 而不是 NLR 或 CLR 对中性粒细胞识别 至关重要。
