沙门氏菌通过髓样分化因子88（MyD88）和肿瘤坏死因子受体1（TNFR1）在体内诱导CD8α(+)树突状细胞死亡，但不诱导CD11c(int)CD11b(+)炎性细胞死亡。

Salmonella induces death of CD8alpha(+) dendritic cells but not CD11c(int)CD11b(+) inflammatory cells in vivo via MyD88 and TNFR1.

作者信息

Sundquist Malin, Wick Mary Jo

机构信息

Department of Microbiology and Immunology, Göteborg University, Göteborg, Sweden.

出版信息

J Leukoc Biol. 2009 Feb;85(2):225-34. doi: 10.1189/jlb.0708413. Epub 2008 Nov 12.

DOI:10.1189/jlb.0708413

Abstract

Dendritic cells (DCs), whose lifespan influences their ability to stimulate the immune system, are potent APCs that are critical for initiating immunity. Here, we show that oral infection with Salmonella enterica serovar Typhimurium induces death of DCs in the gut-draining lymph nodes. Although CD8alpha(+) DCs were sensitive to Salmonella-induced death, CD8alpha(-) DCs and in particular recruited CD11c(int)CD11b(+) inflammatory cells, were resistant. Infecting mice deficient for MyD88 revealed that Salmonella-induced death of CD8alpha(+) DCs was dependent on this adaptor for TLR signaling. In addition, CD8alpha(+) DCs in infected, TNFR1-deficient mice were resistant to Salmonella-induced death. These data, combined with the strict MyD88-dependent production of TNF in Salmonella-infected mice, suggest that MyD88-dependent TNF mediates DC death. As recruited CD11c(int)CD11b(+) cells were resistant to Salmonella-induced death, they could compensate for the infection-induced loss of DCs if they function as APCs. However, in contrast to DCs, CD11c(int)CD11b(+) cells could not present the model antigen OVA expressed in Salmonella to OVA-specific CD4 T cells. These results show that Salmonella induces DC death after oral infection via MyD88 and TNFR1, which could have a negative impact on the initiation of antibacterial immunity.

摘要

树突状细胞（DCs）的寿命会影响其刺激免疫系统的能力，它们是强大的抗原呈递细胞（APCs），对启动免疫至关重要。在此，我们表明，口服感染鼠伤寒沙门氏菌会导致引流肠道的淋巴结中的DCs死亡。虽然CD8α(+) DCs对沙门氏菌诱导的死亡敏感，但CD8α(-) DCs，尤其是募集的CD11c(int)CD11b(+)炎性细胞具有抗性。感染MyD88缺陷小鼠表明，沙门氏菌诱导的CD8α(+) DCs死亡依赖于这种用于Toll样受体（TLR）信号传导的衔接蛋白。此外，感染的TNFR1缺陷小鼠中的CD8α(+) DCs对沙门氏菌诱导的死亡具有抗性。这些数据，结合沙门氏菌感染小鼠中严格依赖MyD88产生的肿瘤坏死因子（TNF），表明依赖MyD88的TNF介导DCs死亡。由于募集的CD11c(int)CD11b(+)细胞对沙门氏菌诱导的死亡具有抗性，如果它们作为APCs发挥作用，它们可以补偿感染诱导的DCs损失。然而，与DCs不同，CD11c(int)CD11b(+)细胞不能将沙门氏菌中表达的模型抗原OVA呈递给OVA特异性CD4 T细胞。这些结果表明，口服感染后沙门氏菌通过MyD88和TNFR1诱导DCs死亡，这可能会对抗菌免疫的启动产生负面影响。