Doyle Sean E, O'Connell Ryan M, Miranda Gustavo A, Vaidya Sagar A, Chow Edward K, Liu Philip T, Suzuki Shinobu, Suzuki Nobutaka, Modlin Robert L, Yeh Wen-Chen, Lane Timothy F, Cheng Genhong
Dept. of Microbiology, Immunology and Molecular Genetics, University of California-Los Angeles, 8-240 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
J Exp Med. 2004 Jan 5;199(1):81-90. doi: 10.1084/jem.20031237. Epub 2003 Dec 29.
Toll-like receptor (TLR) signaling and phagocytosis are hallmarks of macrophage-mediated innate immune responses to bacterial infection. However, the relationship between these two processes is not well established. Our data indicate that TLR ligands specifically promote bacterial phagocytosis, in both murine and human cells, through induction of a phagocytic gene program. Importantly, TLR-induced phagocytosis of bacteria was found to be reliant on myeloid differentiation factor 88-dependent signaling through interleukin-1 receptor-associated kinase-4 and p38 leading to the up-regulation of scavenger receptors. Interestingly, individual TLRs promote phagocytosis to varying degrees with TLR9 being the strongest and TLR3 being the weakest inducer of this process. We also demonstrate that TLR ligands not only amplify the percentage of phagocytes uptaking Escherichia coli, but also increase the number of bacteria phagocytosed by individual macrophages. Taken together, our data describe an evolutionarily conserved mechanism by which TLRs can specifically promote phagocytic clearance of bacteria during infection.
Toll样受体（TLR）信号传导和吞噬作用是巨噬细胞介导的针对细菌感染的固有免疫反应的标志。然而，这两个过程之间的关系尚未完全明确。我们的数据表明，在小鼠和人类细胞中，TLR配体通过诱导吞噬基因程序，特异性地促进细菌吞噬作用。重要的是，发现TLR诱导的细菌吞噬作用依赖于通过白细胞介素-1受体相关激酶-4和p38的髓样分化因子88依赖性信号传导，从而导致清道夫受体的上调。有趣的是，单个TLR促进吞噬作用的程度各不相同，其中TLR9是此过程最强的诱导剂，而TLR3是最弱的诱导剂。我们还证明，TLR配体不仅增加了摄取大肠杆菌的吞噬细胞的百分比，而且还增加了单个巨噬细胞吞噬的细菌数量。综上所述，我们的数据描述了一种进化上保守的机制，通过该机制TLR在感染期间可特异性促进细菌的吞噬清除。
