alpha-Galactosylceramide Promotes Killing of Listeria monocytogenes within the Macrophage Phagosome through Invariant NKT-Cell Activation

作者：Emoto Masashi^*; Yoshida Tomomi; Fukuda Toshio; Kawamura Ikuo; Mitsuyama Masao; Kita Eiji; Hurwitz Robert; Kaufmann Stefan H E; Emoto Yoshiko

来源：Infection and Immunity, 2010, 78(6): 2667-2676.

DOI：10.1128/IAI.01441-09

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 (M phi) participate in the control of microbial pathogens. In the present study, we examined the participation of M phi in immune intervention in infection by alpha-GalCer using a murine model of listeriosis. Phagocytic and bactericidal activities of peritoneal M phi 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 M phi from mice treated with alpha-GalCer, respectively. Although enhanced bactericidal activity of peritoneal M phi 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 M phi 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 M phi activated by IFN-gamma from iNKT cells residing in an organ(s) other than the peritoneal cavity.

• 出版日期2010-6