Rakebrandt Nikolas, Lentes Sabine, Neumann Heinz, James Leo C, Neumann-Staubitz Petra
Institute for Microbiology and Genetics, Georg-August-University Goettingen, Goettingen, Germany.
Pathog Dis. 2014 Nov;72(2):131-7. doi: 10.1111/2049-632X.12192. Epub 2014 Jun 27.
TRIM21 ('tripartite motif-containing protein 21', Ro52) is a ubiquitously expressed cytosolic Fc receptor, which has a potent role in protective immunity against nonenveloped viruses. TRIM21 mediates intracellular neutralisation of antibody-coated viruses, a process called ADIN (antibody-dependent intracellular neutralisation). Our results reveal a similar mechanism to fight bacterial infections. TRIM21 is recruited to the intracellular pathogen Salmonella enterica in epithelial cells early in infection. TRIM21 does not bind directly to S. enterica, but to antibodies opsonising it. Most importantly, bacterial restriction is dependent on TRIM21 as well as on the opsonisation state of the bacteria. Finally, Salmonella and TRIM21 colocalise with the autophagosomal marker LC3, and intracellular defence is enhanced in starved cells suggesting an involvement of the autophagocytic pathway. Our data extend the protective role of TRIM21 from viruses to bacteria and thereby strengthening the general role of ADIN in cellular immunity.
TRIM21（“含三联基序蛋白21”，Ro52）是一种广泛表达的胞质Fc受体，在针对无包膜病毒的保护性免疫中发挥着重要作用。TRIM21介导抗体包被病毒的细胞内中和作用，这一过程称为ADIN（抗体依赖性细胞内中和作用）。我们的研究结果揭示了一种对抗细菌感染的类似机制。在感染早期，TRIM21被募集到上皮细胞内的病原体肠炎沙门氏菌中。TRIM21不直接与肠炎沙门氏菌结合，而是与使其发生调理作用的抗体结合。最重要的是，细菌限制依赖于TRIM21以及细菌的调理状态。最后，沙门氏菌和TRIM21与自噬体标记物LC3共定位，并且在饥饿细胞中细胞内防御增强，这表明自噬途径参与其中。我们的数据将TRIM21的保护作用从病毒扩展到细菌，从而加强了ADIN在细胞免疫中的一般作用。
