title: Alpha-galactosylceramide promotes killing of Listeria monocytogenes within the macrophage phagosome through invariant NKT-cell activation.
abstract: alpha-Galactosylceramide (alpha-GalCer) has been exploited for the treatment of microbial infections. Although amelioration of infection by alpha-GalCer involves invariant natural killer T (iNKT)-cell activation, it remains to be determined whether macrophages (Mphi) participate in the control of microbial pathogens. In the present study, we examined the participation of Mphi in immune intervention in infection by alpha-GalCer using a murine model of listeriosis. Phagocytic and bactericidal activities of peritoneal Mphi from C57BL/6 mice, but not iNKT cell-deficient mice, were enhanced after intraperitoneal injection of alpha-GalCer despite the absence of iNKT cells in the peritoneal cavity. High levels of gamma interferon (IFN-gamma) and nitric oxide (NO) were detected in the peritoneal cavities of mice treated with alpha-GalCer and in culture supernatants of peritoneal Mphi from mice treated with alpha-GalCer, respectively. Although enhanced bactericidal activity of peritoneal Mphi by alpha-GalCer was abrogated by endogenous IFN-gamma neutralization, this was only marginally affected by NO inhibition. Similar results were obtained by using a listeriolysin O-deficient strain of Listeria monocytogenes. Moreover, respiratory burst in Mphi was increased after alpha-GalCer treatment. Our results suggest that amelioration of listeriosis by alpha-GalCer is, in part, caused by enhanced killing of L. monocytogenes within phagosomes of Mphi activated by IFN-gamma from iNKT cells residing in an organ(s) other than the peritoneal cavity.
authors.affiliation: Laboratory of Immunology, Department of Laboratory Sciences, Gunma University School of Health Sciences, Maebashi, Gunma 371-8511, Japan. memoto@health.gunma-u.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Emoto
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukuda
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kawamura
authors.forename: Masao
authors.initials: M
authors.lastname: Mitsuyama
authors.forename: Eiji
authors.initials: E
authors.lastname: Kita
authors.forename: Robert
authors.initials: R
authors.lastname: Hurwitz
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Emoto
mesh_terms: D000818:Animals; D005260:Female; D005699:Galactosylceramides / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D055611:Natural Killer T-Cells / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D010529:Peritoneal Cavity / Q000382:microbiology; D010588:Phagosomes / Q000382:microbiology*; D016897:Respiratory Burst / Q000276:immunology
chemical_list: D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D009569:Nitric Oxide; D007371:Interferon-gamma