NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation.
Sepsis could affect the central nervous system and thus induces neuroinflammation, which subsequently leads to brain damage or dysfunction. However, the mechanisms of generation of neuroinflammation during sepsis remain poorly understood. By administration of lipopolysaccharides (LPS) in mice to mimic sepsis, we found that shortly after opening the blood-brain barrier, conventional CD11b(+)CD27(+) NK subset migrated into the brain followed by subsequent neutrophil infiltration. Interestingly, depletion of NK cells prior to LPS treatment severely impaired neutrophil recruitment in the inflamed brain. By in vivo recruitment assay, we found that brain-infiltrated NK cells displayed chemotactic activity to neutrophils, which depended on the higher expression of chemokines such as CXCL2. Moreover, microglia were also responsible for neutrophil recruitment, and their chemotactic activity was significantly impaired by ablation of NK cells. Furthermore, depletion of NK cells could significantly ameliorate depression-like behavior in LPS-treated mice. These data indicated a NK cell-regulated neutrophil recruitment in the blamed brain, which also could be seen on another sepsis model, cecal ligation and puncture. So, our findings revealed an important scenario in the generation of sepsis-induced neuroinflammation.
Institute of Immunology, Taishan Medical University, Taian, Shandong, 271000, China.
Hao
H
He
Institute of Immunology, Taishan Medical University, Taian, Shandong, 271000, China.
Tingting
T
Geng
Institute of Immunology, Taishan Medical University, Taian, Shandong, 271000, China.
Piyun
P
Chen
Institute of Immunology, Taishan Medical University, Taian, Shandong, 271000, China.
Meixiang
M
Wang
Institute of Immunology, Taishan Medical University, Taian, Shandong, 271000, China.
Jingxia
J
Hu
Institute of Immunology, Taishan Medical University, Taian, Shandong, 271000, China.
Li
L
Kang
Institute of Immunology, Taishan Medical University, Taian, Shandong, 271000, China.
Wengang
W
Song
Institute of Immunology, Taishan Medical University, Taian, Shandong, 271000, China.
Hua
H
Tang
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology*; D002432:Cecum / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D003863:Depression; D005260:Female; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000378:metabolism*; D008026:Ligation; D008070:Lipopolysaccharides; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D011677:Punctures; D018805:Sepsis / Q000150:complications / Q000276:immunology* / Q000473:pathology*
D018925:Chemokines; D008070:Lipopolysaccharides