Lactosylceramide is a Pattern Recognition Receptor that Forms Lyn-Coupled Membrane Microdomains on Neutrophils

Abstract

Over the last 30 years, many studies have indicated that glycosphingolipids expressed on the cell surface may act as binding sites for microorganisms. Based on their physicochemical characteristics, glycosphingolipids form membrane microdomains (lipid rafts) with cholesterol, sphingomyelin glycosylphosphatidylinositol (GPI)-anchored proteins, and various signaling molecules. Among the glycosphingolipids, lactosylceramide (LacCer, CDw17) can bind to various microorganisms, including Bordetella pertussis, Helicobacter pylori, and Candida albicans. LacCer is highly expressed on the plasma membranes of human neutrophils, and forms membrane microdomains associated with the Src family tyrosine kinase Lyn. LacCer-enriched membrane microdomains mediate superoxide generation, chemotaxis, and non-opsonic phagocytosis. Therefore, LacCer-enriched membrane microdomains are thought to function as pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) expressed on microorganisms. Neutrophils express several types of PRR, among which CD11b/CD18-integrin (αM/β2-integrin, CR3, Mac-1) plays a central role in the immunological functions of phagocytes. CD11b/CD18 mediates neutrophil phagocytosis of C3bi-opsonized microorganisms via the binding of CD11b/CD18 with C3bi, while CD11b/CD18 is able to bind to PAMPs as a PRR, and mediates phagocytosis of non-opsonized microorganisms. However, CD11b/CD18 has no signaling motif in the cytoplasm to mediate the outside-in signaling by itself. Therefore, other PRRs or signaling molecules are needed to mediate CD11b/CD18- dependent functions. In this review, we introduce the organization and functions of LacCer-enriched membrane microdomains and the roles of these microdomains in CD11b/CD18-dependent neutrophil phagocytosis of non-opsonized microorganisms. Keywords: Lactosylceramide (LacCer), membrane microdomain, CD11b/CD18, pattern recognition receptor (PRR), pathogen- associated molecular pattern (PAMP), non-opsonic phagocytosis, neutrophil, innate immunity