TLR2-mediated survival of Staphylococcus aureus in macrophages: a novel bacterial strategy against host innate immunity.
TLR2 plays a role as a pattern-recognition receptor in the innate immune response involving secreted proteins against microbial pathogens. To examine its possible involvement in the cellular response, we determined the levels of the engulfment and subsequent killing of bacteria by macrophages prepared from TLR2-deficient and wild-type mice. The level of the engulfment of Staphylococcus aureus or Escherichia coli was almost the same between TLR2-lacking and wild-type macrophages. However, the colony-forming ability of engulfed S. aureus, but not of E. coli, decreased to a greater extent in TLR2-lacking macrophages than in the wild-type control. The incubation with S. aureus caused activation of JNK in wild-type macrophages but not in TLR2-lacking macrophages, and the pretreatment of wild-type macrophages with a JNK inhibitor increased the rate of killing of engulfed S. aureus, but again not of E. coli. In addition, the number of colonies formed by engulfed S. aureus increased in the JNK-dependent manner when TLR2-lacking macrophages were pretreated with LPS. Furthermore, JNK seemed to inhibit the generation of superoxide, not of NO, in macrophages. These results collectively suggested that the level of superoxide is reduced in macrophages that have engulfed S. aureus through the actions of TLR2-activated JNK, resulting in the prolonged survival of the bacterium in phagosomes. The same regulation did not influence the survival of E. coli, because this bacterium was more resistant to superoxide than S. aureus. We propose a novel bacterial strategy for survival in macrophages involving the hijacking of an innate immune receptor.
Watanabe
Ikuko
I
Graduate School of Medical Science, Kanazawa University, Japan.
Ichiki
Manami
M
Shiratsuchi
Akiko
A
Nakanishi
Yoshinobu
Y
D000818:Animals; D007113:Immunity, Innate; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology; D010587:Phagocytosis; D013211:Staphylococcus aureus / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000502:physiology*
C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D013481:Superoxides; D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases