tailieunhanh - The Biology of NKT Cells Albert Bendelac - part 3

Thật thú vị, rất nhiều vi khuẩn khác, đặc biệt là vi khuẩn Gram âm, LPS-dương tính, có thể kích hoạt NKT tế bào. Tuy nhiên, thay vì cung cấp cho NKT của các phối tử như Sphingomonas hoặc Ehrlichia, những vi khuẩn này xuất hiện để kích hoạt phản ứng tế bào autoreactive NKT | Annu. Rev. Immunol. 297-336. Downloaded from by HINARI on 09 21 07. For personal use only. pathogen and member of the Rickettsiales that is of widespread significance for mammals including wild and domesticated ruminants dogs and humans from some regions of the world such as Africa and East Asia. Ehrlichia muris activates NKT cells independently of iGb3 and its clearance was profoundly altered in CD1d- or Ja18-deficient animals 23 . Ehrlichia is a Gram-negative LPS-negative obligate intracellular bacterium whose cell wall composition has not been elucidated. Interestingly many other bacteria particularly the Gram-negative LPS-positive ones can activate NKT cells. However rather than provide their own NKT ligands like Sphin-gomonas or Ehrlichia these bacteria appear to trigger autoreactive NKT cell responses 23 60 . In the case of Salmonella this is suggested by the abrogation of NKT cell activation in the presence of DCs lacking 3 -hexosaminidase B the enzyme responsible for the generation of iGb3 from iGb4 in the Direct microbial recognition lysosome and by blocking experiments with the lectin Griffonia simplicifolia IB4 which recognizes the terminal sugar of the Gala1-3Gal epitope of iGb3 bound to CD1d and blocks NKT cell activation 23 . Strikingly NKT cell activation by Gram-negative LPS-positive Salmonella is absolutely dependent upon TLR signaling through the adaptors MyD88 and Trif and upon IL-12 release by the APC although the precise TLR combination and the corresponding microbial structures involved remain to be determined. Thus the proposed scenario suggests that TLR signaling leading but not limited to IL-12 secretion enhances the ability of DCs to stimulate NKT cells through presentation of endogenous ligands Figure 7 . Whether TLR signaling induces an upregulation of iGb3 or changes in the expression of other factors such as for example NK receptor ligands is unclear. Contrary to an early report 195 NKT cells do not