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.