Pyroptosis of resident macrophages differentially orchestrates inflammatory responses to Staphylococcus aureus in resistant and susceptible mice. Issue 3 (21st January 2015)

• Record Type: Journal Article
• Authors: Accarias, Solène; Lugo‐Villarino, Geanncarlo; Foucras, Gilles; Neyrolles, Olivier; Boullier, Séverine; Tabouret, Guillaume
• Is Part Of: European journal of immunology. Volume 45:Issue 3(2015:Mar.)
• Page Start: 794
• Page End: 806
• Publication Date: 2015-01-21
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201445098
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The relationship between <italic>Staphylococcus aureus</italic> and innate immunity is highly complex and requires further investigation to be deciphered. i.p. challenge of C57BL/6 and DBA/2 mice, resistant and susceptible to the infection, respectively, resulted in different patterns of cytokine production and neutrophil recruitment. <italic>Staphylococcus aureus</italic> infection induced macrophage pyroptosis, an inflammasome‐dependent cell death program, whose rates significantly differed between C57BL/6 and DBA/2 mice. Fast rate pyroptosis of C57BL/6 macrophages released high levels of IL‐1β but limited the synthesis of other cytokines such as TNF‐α, IL‐6, CXCL1, and CXCL2. Conversely, the extended survival of DBA/2 macrophages allowed substantial production of these NF‐κB‐related cytokines. Phenotyping of resting macrophages in different mouse strains revealed differential predisposition toward specific macrophage phenotypes that modulate <italic>S. aureus</italic>‐mediated inflammasome activation. Treatment of DBA/2 susceptible mice with inflammasome inducers (i.e. nigericin and ATP) artificially increased pyroptosis and lowered the levels of NF‐κB‐related inflammatory cytokines, but restored IL‐1β to levels similar to those in C57BL/6 mice. Collectively, this study promotes the concept that, in association with host genetics, the basal phenotype of resident macrophages influences the early inflammatory response and possibly participates in <italic>S. aureus</italic> infection outcome via the inflammasome pathway and subsequent pyroptosis.</p> </abstract>