Macrophage mediated recognition and clearance of Borrelia burgdorferi elicits MyD88-dependent and -independent phagosomal signals that contribute to phagocytosis and inflammation.
Macrophage mediated recognition and clearance of Borrelia burgdorferi elicits MyD88-dependent and -independent phagosomal signals that contribute to phagocytosis and inflammation.
复制标题
DOI：
10.1186/s12865-021-00418-8
复制
发表时间：
2021-05-17
期刊：
影响因子：
3
通讯作者：
Salazar JC
中科院分区：
文献类型：
--
作者：
Benjamin SJ;Hawley KL;Vera-Licona P;La Vake CJ;Cervantes JL;Ruan Y;Radolf JD;Salazar JC
巨噬细胞在细菌识别和清除中发挥重要作用，包括莱姆病螺旋体伯氏疏螺旋体（Bb）。为了阐明MyD 88/TLR信号增强巨噬细胞清除Bb的机制，我们研究了野生型（WT）和MyD 88-/-Bb刺激的骨髓源性巨噬细胞（BMDM）。MyD 88 −/− BMDM表现出螺旋体摄取受损，但在螺旋体内化后吞噬体相当成熟。对感染的WT和MyD 88 −/− BMDM进行RNA测序，发现了一大群差异表达的MyD 88依赖性基因，这些基因与吞噬过程中肌动蛋白和细胞骨架的重组相关，沿着几种与炎症细胞募集相关的MyD 88非依赖性趋化因子。我们计算生成的网络，确定了几个MyD 88依赖的中间蛋白（Rhoq和Cyfip 1），已知分别介导炎症和吞噬作用。我们的研究结果表明，MyD 88信号增强，但不是必需的，细菌摄取或吞噬体成熟，并提供机制的见解MyD 88介导的吞噬体信号增强Bb的摄取和清除。在线版本包含补充材料，可通过10.1186/s12865-021-00418-8获取。
Macrophages play prominent roles in bacteria recognition and clearance, including Borrelia burgdorferi (Bb), the Lyme disease spirochete. To elucidate mechanisms by which MyD88/TLR signaling enhances clearance of Bb by macrophages, we studied wildtype (WT) and MyD88−/− Bb-stimulated bone marrow-derived macrophages (BMDMs). MyD88−/− BMDMs exhibit impaired uptake of spirochetes but comparable maturation of phagosomes following internalization of spirochetes. RNA-sequencing of infected WT and MyD88−/− BMDMs identified a large cohort of differentially expressed MyD88-dependent genes associated with re-organization of actin and cytoskeleton during phagocytosis along with several MyD88-independent chemokines involved in inflammatory cell recruitment. We computationally generated networks which identified several MyD88-dependent intermediate proteins (Rhoq and Cyfip1) that are known to mediate inflammation and phagocytosis respectively. Our findings show that MyD88 signaling enhances, but is not required, for bacterial uptake or phagosomal maturation and provide mechanistic insights into how MyD88-mediated phagosomal signaling enhances Bb uptake and clearance. The online version contains supplementary material available at 10.1186/s12865-021-00418-8.
登录
查看更多内容
影响因子：
4.9
作者：
Shin JJ;Strle K;Glickstein LJ;Luster AD;Steere AC
通讯作者：
Steere AC
影响因子：
56.9
作者：
Blander, JM;Medzhitov, R
通讯作者：
Medzhitov, R
DOI：
10.1073/pnas.1013776108
发表时间：
2011-03-01
影响因子：
11.1
作者：
Cervantes, Jorge L.;Dunham-Ems, Star M.;Salazar, Juan C.
通讯作者：
Salazar, Juan C.
影响因子：
4.4
作者：
Behera, Aruna K.;Hildebrand, Ethan;Hu, Linden T.
通讯作者：
Hu, Linden T.
影响因子：
4.4
作者：
Edelson, BT;Unanue, ER
通讯作者：
Unanue, ER