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...

Full description

Bibliographic Details
Main Authors: Maria Klezovich-Bénard, Jean-Philippe Corre, Hélène Jusforgues-Saklani, Daniel Fiole, Nick Burjek, Jean-Nicolas Tournier, Pierre L Goossens
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC3257302?pdf=render
_version_ 1818297890886385664
author Maria Klezovich-Bénard
Jean-Philippe Corre
Hélène Jusforgues-Saklani
Daniel Fiole
Nick Burjek
Jean-Nicolas Tournier
Pierre L Goossens
author_facet Maria Klezovich-Bénard
Jean-Philippe Corre
Hélène Jusforgues-Saklani
Daniel Fiole
Nick Burjek
Jean-Nicolas Tournier
Pierre L Goossens
author_sort Maria Klezovich-Bénard
collection DOAJ
description 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.
first_indexed 2024-12-13T04:26:38Z
format Article
id doaj.art-e1c1fb993f5a42baaf3497911735224d
institution Directory Open Access Journal
issn 1553-7366
1553-7374
language English
last_indexed 2024-12-13T04:26:38Z
publishDate 2012-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Pathogens
spelling doaj.art-e1c1fb993f5a42baaf3497911735224d2022-12-21T23:59:40ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-0181e100248110.1371/journal.ppat.1002481Mechanisms of NK cell-macrophage Bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins.Maria Klezovich-BénardJean-Philippe CorreHélène Jusforgues-SaklaniDaniel FioleNick BurjekJean-Nicolas TournierPierre L GoossensNK 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.http://europepmc.org/articles/PMC3257302?pdf=render
spellingShingle Maria Klezovich-Bénard
Jean-Philippe Corre
Hélène Jusforgues-Saklani
Daniel Fiole
Nick Burjek
Jean-Nicolas Tournier
Pierre L Goossens
Mechanisms of NK cell-macrophage Bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins.
PLoS Pathogens
title Mechanisms of NK cell-macrophage Bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins.
title_full Mechanisms of NK cell-macrophage Bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins.
title_fullStr Mechanisms of NK cell-macrophage Bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins.
title_full_unstemmed Mechanisms of NK cell-macrophage Bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins.
title_short Mechanisms of NK cell-macrophage Bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins.
title_sort mechanisms of nk cell macrophage bacillus anthracis crosstalk a balance between stimulation by spores and differential disruption by toxins
url http://europepmc.org/articles/PMC3257302?pdf=render
work_keys_str_mv AT mariaklezovichbenard mechanismsofnkcellmacrophagebacillusanthraciscrosstalkabalancebetweenstimulationbysporesanddifferentialdisruptionbytoxins
AT jeanphilippecorre mechanismsofnkcellmacrophagebacillusanthraciscrosstalkabalancebetweenstimulationbysporesanddifferentialdisruptionbytoxins
AT helenejusforguessaklani mechanismsofnkcellmacrophagebacillusanthraciscrosstalkabalancebetweenstimulationbysporesanddifferentialdisruptionbytoxins
AT danielfiole mechanismsofnkcellmacrophagebacillusanthraciscrosstalkabalancebetweenstimulationbysporesanddifferentialdisruptionbytoxins
AT nickburjek mechanismsofnkcellmacrophagebacillusanthraciscrosstalkabalancebetweenstimulationbysporesanddifferentialdisruptionbytoxins
AT jeannicolastournier mechanismsofnkcellmacrophagebacillusanthraciscrosstalkabalancebetweenstimulationbysporesanddifferentialdisruptionbytoxins
AT pierrelgoossens mechanismsofnkcellmacrophagebacillusanthraciscrosstalkabalancebetweenstimulationbysporesanddifferentialdisruptionbytoxins