Synergistic Costimulatory Effect of Chlamydia pneumoniae with Carbon Nanoparticles on NLRP3 Inflammasome-Mediated Interleukin-1β Secretion in Macrophages.
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-1β (IL-1β) is a critical player in the pathogenesis of asthma. C. pneumoniae induces IL-1β 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-1β secretion from lipopolysaccharide-primed macrophages. This study assessed whether costimulation of C. pneumoniae with CNTs synergistically enhanced IL-1β secretion from macrophages, and determined the molecular mechanism involved. Enhanced IL-1β 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-1β secretion. Gene silencing using small interfering RNA (siRNA) targeting the NLRP3 gene also abolished IL-1β secretion. Other inhibitors (K(+) efflux inhibitor, cathepsin B inhibitor, and reactive oxygen species-generating inhibitor) also blocked IL-1β secretion. Taken together, these findings demonstrated that CNTs synergistically enhanced IL-1β 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.
Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
Junji
J
Matsuo
Division of Biomedical Imaging Research, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Shinji
S
Nakamura
Health Innovation and Technology Center, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
Seiji
S
Takeda
Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan Japan Society for the Promotion of Science, Tokyo, Japan.
Kasumi
K
Ishida
Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan Japan Society for the Promotion of Science, Tokyo, Japan.
Tomohiro
T
Yamazaki
Division of Ultrastructural Research, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Mitsutaka
M
Yoshida
Health Innovation and Technology Center, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan Department of Health Science Technology, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
Hitoshi
H
Chiba
Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan Health Innovation and Technology Center, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
Shu-Ping
SP
Hui
Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan hiroyuki@med.hokudai.ac.jp.
Hiroyuki
H
Yamaguchi
D002244:Carbon / Q000276:immunology*; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D004705:Endocytosis; D020868:Gene Silencing; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D046529:Microscopy, Electron, Transmission; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D053758:Nanoparticles / Q000378:metabolism*
D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D002244:Carbon; D020170:Caspase 1