NK T cells stimulated with a ligand for TLR2 at least partly contribute to liver injury caused by Escherichia coli infection in mice.
Fas ligand (Fas L) expression was induced on intrahepatic NK1.1(+) T cells in vivo after an intraperitoneal inoculation of Escherichia coli. Liver injury after E. coli infection, as assessed by serum GPT level and histological examination, was significantly reduced in Jalpha281(-/-) mice lacking NK1.1(+) T cells or in gld/gld mice bearing mutated Fas L, indicating that NK T cells at least partly contribute to E. coli-induced liver injury in a Fas/Fas L-dependent manner. Bacterial numbers in organs and cytokine levels in serum of Jalpha281(-/-) mice did not differ from those of Jalpha281(+/+) mice following E. coli infection. Intrahepatic NK1.1(+) T cells, which preferentially expressed Toll-like receptor 2 (TLR2) mRNA, responded in vitro to synthetic lipoprotein, a ligand for TLR2, by inducing Fas L expression on their surface. In a manner analogous to E. coli infection, lipoprotein and LPS could additively induce Fas L expression on NK1.1(+) T cells, leading to liver injury in vivo in normal mice but not in gld/gld mice. In conclusion, it is suggested that induction of Fas L on NK T cells in response to bacterial components such as lipoproteins plays an important role in pathogenesis of E. coli-induced liver injury in mice.
Hiromatsu
Takashi
T
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya, Japan. takasi-h@med.nagoya-u.ac.jp
Matsuguchi
Tetsuya
T
Shimizu
Hideyuki
H
Yajima
Toshiki
T
Nishimura
Hitoshi
H
Arai
Toshiyuki
T
Nimura
Yuji
Y
Yoshikai
Yasunobu
Y
D000818:Animals; D016207:Cytokines / Q000097:blood; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000378:metabolism / Q000473:pathology; D053222:Fas Ligand Protein; D007694:Killer Cells, Natural / Q000378:metabolism*; D008024:Ligands; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors