Edema Toxin Impairs Anthracidal Phospholipase A2 Expression by Alveolar Macrophages

PLoS Pathogens

Lucas Ravaux¹  Benoit Raymond¹  Michel Raymondjean¹  Lhousseine Touqui²  Thomas Candela³  Dominique Leduc⁴  Ronan Le Goffic⁴  Pierre Louis Goossens⁴ 

[1] Institut Pasteur, Unité de Défense Innée et Inflammation, Paris, France;Institut Pasteur, Unité des Toxines et Pathogénie Bactérienne, Paris, France;UMR 7079, Physiologie et Physiopathologie Université Pierre et Marie Curie, CNRS, Paris, France;Unité Inserm, U.874, Paris, France

关键词: Bacillus anthracis;    Bacterial spores;    Transcription factors;    Secretion;    Respiratory infections;    Anthrax;    Guinea pigs;    Toxins;   

DOI  :  10.1371/journal.ppat.0030187

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Bacillus anthracis, the etiological agent of anthrax, is a spore-forming Gram-positive bacterium. Infection with this pathogen results in multisystem dysfunction and death. The pathogenicity of B. anthracis is due to the production of virulence factors, including edema toxin (ET). Recently, we established the protective role of type-IIA secreted phospholipase A2 (sPLA2-IIA) against B. anthracis. A component of innate immunity produced by alveolar macrophages (AMs), sPLA2-IIA is found in human and animal bronchoalveolar lavages at sufficient levels to kill B. anthracis. However, pulmonary anthrax is almost always fatal, suggesting the potential impairment of sPLA2-IIA synthesis and/or action by B. anthracis factors. We investigated the effect of purified ET and ET-deficient B. anthracis strains on sPLA2-IIA expression in primary guinea pig AMs. We report that ET inhibits sPLA2-IIA expression in AMs at the transcriptional level via a cAMP/protein kinase A–dependent process. Moreover, we show that live B. anthracis strains expressing functional ET inhibit sPLA2-IIA expression, whereas ET-deficient strains induced this expression. This stimulatory effect, mediated partly by the cell wall peptidoglycan, can be counterbalanced by ET. We conclude that B. anthracis down-regulates sPLA2-IIA expression in AMs through a process involving ET. Our study, therefore, describes a new molecular mechanism implemented by B. anthracis to escape innate host defense. These pioneering data will provide new molecular targets for future intervention against this deathly pathogen.

【 授权许可】

CC BY