Synergistic Costimulatory Effect of Chlamydia pneumoniae with Carbon Nanoparticles on NLRP3 Inflammasome-Mediated Interleukin-1ß Secretion in Macrophages.
Infect Immun
; 83(7): 2917-25, 2015 Jul.
Article
en En
| MEDLINE
| ID: mdl-25939513
The obligate intracellular bacterium Chlamydia pneumoniae is not only a causative agent of community-acquired pneumonia but is also associated with a more serious chronic disease, asthma, which might be exacerbated by air pollution containing carbon nanoparticles. Although a detailed mechanism of exacerbation remains unknown, the proinflammatory cytokine interleukin-1ß (IL-1ß) is a critical player in the pathogenesis of asthma. C. pneumoniae induces IL-1ß in macrophages via NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activation and Toll-like receptor 2/4 (TLR2/4) stimulation. Carbon nanoparticles, such as carbon nanotubes (CNTs), can also evoke the NLRP3 inflammasome to trigger IL-1ß secretion from lipopolysaccharide-primed macrophages. This study assessed whether costimulation of C. pneumoniae with CNTs synergistically enhanced IL-1ß secretion from macrophages, and determined the molecular mechanism involved. Enhanced IL-1ß secretion from C. pneumoniae-infected macrophages by CNTs was dose and time dependent. Transmission electron microscopy revealed that C. pneumoniae and CNTs were engulfed concurrently by macrophages. Inhibitors of actin polymerization or caspase-1, a component of the inflammasome, significantly blocked IL-1ß secretion. Gene silencing using small interfering RNA (siRNA) targeting the NLRP3 gene also abolished IL-1ß secretion. Other inhibitors (K(+) efflux inhibitor, cathepsin B inhibitor, and reactive oxygen species-generating inhibitor) also blocked IL-1ß secretion. Taken together, these findings demonstrated that CNTs synergistically enhanced IL-1ß secretion from C. pneumoniae-infected macrophages via the NLRP3 inflammasome and caspase-1 activation, providing novel insight into our understanding of how C. pneumoniae infection can exacerbate asthma.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carbono
/
Proteínas Portadoras
/
Chlamydophila pneumoniae
/
Interleucina-1beta
/
Nanopartículas
/
Inflamasomas
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Macrófagos
Límite:
Humans
Idioma:
En
Revista:
Infect Immun
Año:
2015
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos