PURPOSE: alpha-Galactosylceramide (alpha-GalCer), which is a specific ligand for CD1d restricted variable-alpha14chain natural killer T cells, has an important role in host defense against a range of microbial infections. We examined whether alpha-GalCer mediates bacterial clearance in a murine urinary tract infection (UTI) model. MATERIALS AND METHODS: The murine UTI model was established by intravesical inoculation of Escherichia coli, Pseudomonas aeruginosa or methicillin resistant Staphylococcus aureus, followed by clamping the distal end of the urethra of C57BL/6 female mice for 4 hours. The antibacterial effect of alpha-GalCer was assessed by comparing the number of cfu/gm kidney tissue 4 days after bacterial inoculation. The prophylactic effect of alpha-GalCer was examined by administrating 3 doses of intraperitoneal alpha-GalCer on alternate days 24 hours before E. coli inoculation. The therapeutic effect of alpha-GalCer was tested by the administration of 2 doses of intraperitoneal alpha-GalCer after bacterial inoculation. To assess cytokine induction by alpha-GalCer serum levels of interleukin-12, interferon-gamma and tumor necrosis factor-alpha were measured by cytometric bead array assay. RESULTS: When administered before bacterial inoculation, alpha-GalCer showed a strong prophylactic antibacterial effect. alpha-GalCer also showed a marked antibacterial effect on preestablished mice UTI caused by E. coli, P. aeruginosa and methicillin resistant S. aureus. alpha-GalCer induced a significantly higher level of interleukin-12, interferon-gamma and tumor necrosis factor-alpha compared with control glycolipids. CONCLUSIONS: These findings suggest a significant role for alpha-GalCer in regulating antibacterial functions by activating natural killer T cells in the murine UTI model.
PURPOSE:alpha-Galactosylceramide (alpha-GalCer), which is a specific ligand for CD1d restricted variable-alpha14chain natural killer T cells, has an important role in host defense against a range of microbial infections. We examined whether alpha-GalCer mediates bacterial clearance in a murineurinary tract infection (UTI) model. MATERIALS AND METHODS: The murine UTI model was established by intravesical inoculation of Escherichia coli, Pseudomonas aeruginosa or methicillin resistant Staphylococcus aureus, followed by clamping the distal end of the urethra of C57BL/6 female mice for 4 hours. The antibacterial effect of alpha-GalCer was assessed by comparing the number of cfu/gm kidney tissue 4 days after bacterial inoculation. The prophylactic effect of alpha-GalCer was examined by administrating 3 doses of intraperitoneal alpha-GalCer on alternate days 24 hours before E. coli inoculation. The therapeutic effect of alpha-GalCer was tested by the administration of 2 doses of intraperitoneal alpha-GalCer after bacterial inoculation. To assess cytokine induction by alpha-GalCer serum levels of interleukin-12, interferon-gamma and tumor necrosis factor-alpha were measured by cytometric bead array assay. RESULTS: When administered before bacterial inoculation, alpha-GalCer showed a strong prophylactic antibacterial effect. alpha-GalCer also showed a marked antibacterial effect on preestablished mice UTI caused by E. coli, P. aeruginosa and methicillin resistant S. aureus. alpha-GalCer induced a significantly higher level of interleukin-12, interferon-gamma and tumor necrosis factor-alpha compared with control glycolipids. CONCLUSIONS: These findings suggest a significant role for alpha-GalCer in regulating antibacterial functions by activating natural killer T cells in the murine UTI model.
Authors: Loreto Parga-Vidal; Michiel C van Aalderen; Regina Stark; Klaas P J M van Gisbergen Journal: Nat Rev Nephrol Date: 2022-01-25 Impact factor: 28.314
Authors: Jakub Kwiecinski; Sara Rhost; Linda Löfbom; Maria Blomqvist; Jan Eric Månsson; Susanna L Cardell; Tao Jin Journal: Infect Immun Date: 2013-01-22 Impact factor: 3.441
Authors: Gabriela Mora-Bau; Andrew M Platt; Nico van Rooijen; Gwendalyn J Randolph; Matthew L Albert; Molly A Ingersoll Journal: PLoS Pathog Date: 2015-07-16 Impact factor: 6.823