Mechanisms of NK Cell-Macrophage Bacillus anthracis Crosstalk: A Balance between Stimulation by Spores and Differential Disruption by Toxins

NK cells are important immune effectors for preventing microbial invasion and dissemination, through natural cytotoxicity and cytokine secretion. Bacillus anthracis spores can efficiently drive IFN-γ production by NK cells. The present study provides insights into the mechanisms of cytokine and cell...

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Bibliographic Details
Published in:	PLoS pathogens Vol. 8; no. 1; p. e1002481
Main Authors:	Klezovich-Bénard, Maria, Corre, Jean-Philippe, Jusforgues-Saklani, Hélène, Fiole, Daniel, Burjek, Nick, Tournier, Jean-Nicolas, Goossens, Pierre L.
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 01.01.2012 Public Library of Science (PLoS)
Subjects:	Animals Bacillus anthracis Bacillus anthracis - immunology Bacterial infections Bacterial Toxins - pharmacology Biology Bordetella pertussis Cell interaction Cells Cells, Cultured Cytotoxicity Edema Female Homeostasis - drug effects Homeostasis - immunology Immune system Immunity, Cellular - drug effects Immunity, Cellular - immunology Immunology Infections Killer cells Killer Cells, Natural - drug effects Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Macrophage Activation - drug effects Macrophage Activation - immunology Macrophages Macrophages - drug effects Macrophages - immunology Macrophages - metabolism Mice Mice, Inbred C57BL Mice, Transgenic Physiological aspects Proteins Receptor Cross-Talk - drug effects Receptor Cross-Talk - immunology Spores (Bacteria) Spores, Bacterial - immunology Spores, Bacterial - physiology Toxins France
ISSN:	1553-7374, 1553-7366, 1553-7374
Online Access:	Get full text
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Summary:	NK cells are important immune effectors for preventing microbial invasion and dissemination, through natural cytotoxicity and cytokine secretion. Bacillus anthracis spores can efficiently drive IFN-γ production by NK cells. The present study provides insights into the mechanisms of cytokine and cellular signaling that underlie the process of NK-cell activation by B. anthracis and the bacterial strategies to subvert and evade this response. Infection with non-toxigenic encapsulated B. anthracis induced recruitment of NK cells and macrophages into the mouse draining lymph node. Production of edema (ET) or lethal (LT) toxin during infection impaired this cellular recruitment. NK cell depletion led to accelerated systemic bacterial dissemination. IFN-γ production by NK cells in response to B. anthracis spores was: i) contact-dependent through RAE-1-NKG2D interaction with macrophages; ii) IL-12, IL-18, and IL-15-dependent, where IL-12 played a key role and regulated both NK cell and macrophage activation; and iii) required IL-18 for only an initial short time window. B. anthracis toxins subverted both NK cell essential functions. ET and LT disrupted IFN-γ production through different mechanisms. LT acted both on macrophages and NK cells, whereas ET mainly affected macrophages and did not alter NK cell capacity of IFN-γ secretion. In contrast, ET and LT inhibited the natural cytotoxicity function of NK cells, both in vitro and in vivo. The subverting action of ET thus led to dissociation in NK cell function and blocked natural cytotoxicity without affecting IFN-γ secretion. The high efficiency of this process stresses the impact that this toxin may exert in anthrax pathogenesis, and highlights a potential usefulness for controlling excessive cytotoxic responses in immunopathological diseases. Our findings therefore exemplify the delicate balance between bacterial stimulation and evasion strategies. This highlights the potential implication of the crosstalk between host innate defences and B. anthracis in initial anthrax control mechanisms.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Conceived and designed the experiments: MKB PLG JPC HJS JNT DF. Performed the experiments: MKB JPC NB PLG DF. Analyzed the data: MKB JPC HJS NB DF JNT PLG. Contributed reagents/materials/analysis tools: HJS JNT. Wrote the paper: MKB PLG.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1002481