Innate Immune Interactions between Bacillus anthracis and Host Neutrophils

• Published in: Frontiers in cellular and infection microbiology Vol. 8; p. 2
• Main Authors: Liu, Janet Z, Ali, Syed R, Bier, Ethan, Nizet, Victor
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22.01.2018
• Subjects: Animals; anthrax; Anthrax - immunology; Anthrax - metabolism; Anthrax - microbiology; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Bacillus anthracis; Bacillus anthracis - genetics; Bacillus anthracis - immunology; Bacterial Toxins - genetics; Bacterial Toxins - immunology; Cytokines - metabolism; Cytotoxicity, Immunologic; Disease Models, Animal; edema toxin; Extracellular Traps - immunology; Extracellular Traps - microbiology; Female; Gene Expression Regulation, Bacterial; Host-Pathogen Interactions - immunology; Immunity, Innate; innate immunity; lethal toxin; Mice; Microbiology; neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Neutrophils - microbiology; Phagocytosis - immunology; Bacillus anthracis; host-pathogen interactions; neutrophil extracellular traps; innate immunity; edema toxin; anthrax; neutrophils; lethal toxin
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2018.00002

, the causative agent of anthrax, has been a focus of study in host-pathogen dynamics since the nineteenth century. While the interaction between anthrax and host macrophages has been extensively modeled, comparatively little is known about the effect of anthrax on the immune function of neutrophils, a key frontline effector of innate immune defense. Here we showed that depletion of neutrophils significantly enhanced mortality in a systemic model of anthrax infection in mice. , we found that freshly isolated human neutrophils can rapidly kill anthrax, with specific inhibitor studies showing that phagocytosis and reactive oxygen species (ROS) generation contribute to this efficient bacterial clearance. Anthrax toxins, comprising lethal toxin (LT) and edema toxin (ET), are known to have major roles in macrophage resistance and systemic toxicity. Employing isogenic wild-type and mutant toxin-deficient strains, we show that despite previous studies that reported inhibition of neutrophil function by purified LT or ET, endogenous production of these toxins by live vegetative failed to alter key neutrophil functions. The lack of alteration in neutrophil function is accompanied by rapid killing of by neutrophils, regardless of the bacteria's expression of anthrax toxins. Lastly, our study demonstrates for the first time that anthrax induced neutrophil extracellular trap (NET) formation.