Anthrax Lethal Toxin-Mediated Killing of Human and Murine Dendritic Cells Impairs the Adaptive Immune Response

PLoS Pathogens

Jürgen Brojatsch¹  Steven A Porcelli¹  Abdelkrim Alileche¹  Stefan M Muehlbauer¹  Evan R Serfass¹ 

[1] Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America

关键词: Apoptosis;    Macrophages;    Anthrax;    Flow cytometry;    MTT assay;    Toxins;    Immune response;    Colorimetric assays;   

DOI  :  10.1371/journal.ppat.0010019

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Many pathogens have acquired strategies to combat the immune response. Bacillus anthracis interferes with host defenses by releasing anthrax lethal toxin (LT), which inactivates mitogen-activated protein kinase pathways, rendering dendritic cells (DCs) and T lymphocytes nonresponsive to immune stimulation. However, these cell types are considered resistant to killing by LT. Here we show that LT kills primary human DCs in vitro, and murine DCs in vitro and in vivo. Kinetics of LT-mediated killing of murine DCs, as well as cell death pathways induced, were dependent upon genetic background: LT triggered rapid necrosis in BALB/c-derived DCs, and slow apoptosis in C57BL/6-derived DCs. This is consistent with rapid and slow killing of LT-injected BALB/c and C57BL/6 mice, respectively. We present evidence that anthrax LT impairs adaptive immunity by specifically targeting DCs. This may represent an immune-evasion strategy of the bacterium, and contribute to anthrax disease progression. We also established that genetic background determines whether apoptosis or necrosis is induced by LT. Finally, killing of C57BL/6-derived DCs by LT mirrors that of human DCs, suggesting that C57BL/6 DCs represent a better model system for human anthrax than the prototypical BALB/c macrophages.

【 授权许可】

CC BY