title: Group A Streptococcus induces less p65 nuclear translocation and non-classical nuclear factor kappa B activation in macrophages, which possibly leads to a weaker inflammatory response.
abstract: OBJECTIVE
  The aim of this study was to explore the pathogenic mechanism of group A Streptococcus (GAS) and to investigate how GAS evades phagocytosis by immune cells.
  
  
  METHODS
  The classical inflammatory signaling pathway of macrophages infected with GAS was investigated by protein microarray, real-time PCR, Western blot, immunoprecipitation, and flow cytometry.
  
  
  RESULTS
  GAS induced a lower level of inflammatory mediators in macrophages than either the Gram-positive Staphylococcus aureus or the Gram-negative Escherichia coli. Therefore, the conventional inflammatory signal pathway was investigated. It was found that GAS and S. aureus induced both toll-like receptor (TLR)2 and TLR4 expression, while Gram-negative E. coli only activated TLR4 in RAW264.7 cells. Although MyD88, the main adaptor protein, was activated by the three pathogens, there was no difference in MyD88 expression in macrophages. Nuclear factor kappa B (NF-κB) is the classical transcription factor of inflammatory signals, and the results of the present study showed that GAS, similar to E. coli, induced a weaker p65 nuclear translocation compared to S. aureus. Interestingly, GAS activated NF-κB by inducing p65-p52 heterodimer, but not the classical heterodimer of NF-κB (p65-p50), while E. coli activated NF-κB by inducing both p65-p50 and p65-p52 heterodimers.
  
  
  CONCLUSIONS
  Compared to S. aureus and E. coli infection, GAS induced a weaker nuclear translocation and distinct combination of NF-κB subunits in macrophages, which probably leads to a weak inflammatory response.
authors: Department of Immunology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, China; Department of Pathogeny, Biology and Immunology, School of Basic Medicine, Hebei College of Traditional Chinese Medicine, Shijiazhuang, Hebei, China.
authors: Shuhui
authors: S
authors: Wu
authors: Department of Immunology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, China.
authors: Cuiqing
authors: C
authors: Ma
authors: Department of Immunology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, China.
authors: Xue
authors: X
authors: Gao
authors: Department of Immunology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, China.
authors: Ling
authors: L
authors: Zhang
authors: Department of Immunology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, China.
authors: Qingfeng
authors: Q
authors: Miao
authors: Department of Immunology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, China.
authors: Miao
authors: M
authors: Li
authors: Department of Immunology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, China.
authors: Wenjian
authors: W
authors: Li
authors: Department of Immunology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, China.
authors: Xiaotian
authors: X
authors: Song
authors: Department of Immunology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, China.
authors: Xiurong
authors: X
authors: Wang
authors: Division of Infectious Diseases, Allergy and Immunology, Departments of Internal Medicine and Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
authors: Jianguo
authors: J
authors: Liu
authors: Department of Immunology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei 050017, China. Electronic address: weilin501@163.com.
authors: Lin
authors: L
authors: Wei
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D016328:NF-kappa B / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013211:Staphylococcus aureus; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000472:pathogenicity; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D051996:Transcription Factor RelA
keywords: Group A Streptococcus (GAS); Macrophage; NF-κB; Proinflammatory cytokines