Alpha-GalCer ameliorates listeriosis by accelerating infiltration of Gr-1+ cells into the liver.
Alpha-galactosylceramide (alpha-GalCer) activates invariant (i)NKT cells, which in turn stimulate immunocompetent cells. Although activation of iNKT cells appears critical for regulation of immune responses, it remains elusive whether protection against intracellular bacteria can be induced by alpha-GalCer. Here, we show that alpha-GalCer treatment ameliorates murine listeriosis, and inhibits inflammation following Listeria monocytogenes infection. Liver infiltration of Gr-1+ cells and gamma/delta T cells was accelerated by alpha-GalCer treatment. Gr-1+ cell and gamma/delta T-cell depletion exacerbated listeriosis in alpha-GalCer-treated mice, and this effect was more pronounced after depletion of Gr-1+ cells than that of gamma/delta T cells. Although GM-CSF and IL-17 were secreted by NKT cells after alpha-GalCer treatment, liver infiltration of Gr-1+ cells was not prevented by neutralizing mAb. In parallel to the numerical increase of CD11b+Gr-1+ cells in the liver following alpha-GalCer treatment, CD11b-Gr-1+ cells were numerically reduced in the bone marrow. In addition, respiratory burst in Gr-1+ cells was enhanced by alpha-GalCer treatment. Our results indicate that alpha-GalCer-induced antibacterial immunity is caused, in part, by accelerated infiltration of Gr-1+ cells and to a lesser degree of gamma/delta T cells into the liver. We also suggest that the infiltration of Gr-1+ cells is caused by an accelerated supply from the bone marrow.
Emoto
Masashi
M
Laboratory of Immunology, Department of Laboratory Sciences, Gunma University School of Health Sciences, Maebashi, Gunma, Japan. memoto@health.gunma-u.ac.jp
Emoto
Yoshiko
Y
Yoshizawa
Izumi
I
Kita
Eiji
E
Shimizu
Takamitsu
T
Hurwitz
Robert
R
Brinkmann
Volker
V
Kaufmann
Stefan H E
SH
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology / Q000627:therapeutic use*; D007113:Immunity, Innate; D008088:Listeriosis / Q000188:drug therapy* / Q000276:immunology; D008099:Liver / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology; D009928:Organ Specificity; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D019707:Receptors, Chemokine / Q000032:analysis*; D016897:Respiratory Burst / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D000276:Adjuvants, Immunologic; D005699:Galactosylceramides; C503133:Gr-1 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019707:Receptors, Chemokine; C493154:alpha-galactosylceramide