[Lactosylceramide-enriched Lipid Raft-mediated Infection Immunity]

More than 100 years have passed since Elie Metchnikoff discovered phagocytes. As molecular biological techniques have been developed and improved, we have gained deeper knowledge about the molecular mechanisms of immunological responses to invasion. The innate immune system is the inborn defense mechanism and the first line of defense against all kinds of pathogenic organisms, including bacteria, fungi, viruses, etc. Innate immunity was originally considered to comprise non-specific reactions. However, we now know that innate immune systems develop molecular mechanisms specific to pathogenic microorganisms. In the 1970s, a neutral glycosphingolipid lactosylceramide (LacCer) was found to bind specifically to several kinds of microorganisms. LacCer is highly expressed in phagocytes and epithelial cells. LacCer forms lipid rafts on human neutrophils and is involved in neutrophil migration, phagocytosis, and superoxide generation. In contrast, mouse neutrophils express relatively little LacCer on their cell surfaces. Thus, it is difficult to observe LacCer-mediated innate immunological reactions in mice. Mycobacterium tuberculosis is a typical pathogen for humans but not mice in general. Interestingly, M. tuberculosis can escape killing by neutrophils through regulation of the LacCer-enriched lipid raft-mediated immunological reactions of these cells. These observations indicate that LacCer-enriched lipid rafts play an essential role in human innate immunity. This review describes LacCer-mediated innate immunity in humans.