Although some fungal polysaccharides can induce protective antibodies, they do so very poorly

Although some fungal polysaccharides can induce protective antibodies, they do so very poorly. against infectious disease, but are also involved in host housekeeping functions and can suppress allergic disease. Despite the reactivity of these antibodies to glycans shared between microorganisms and host, diverse tolerance-inducing mechanisms permit the B cell precursors of these antibody-secreting cells to exist within the normal B cell repertoire. Open in a separate window Physique 1 Overlapping expression of conserved glycan epitopes shared among mammalian cells, bacteria, fungi, and allergens and mechanisms by which autoreactive B cells are managed in the B cell repertoire(A) (Group A streptococcus) expresses GlcNAc, which is also expressed by in the form of chitin. (B) Sialyl-lacto-N-tetraose is found on (Group B streptococcus), and in breast milk, which promotes the growth of commensal gut organisms. (C) Some commensal enteric organisms express -1,3-glucan, which is also expressed by German cockroach ((dust mite) (cockroach) Other chitin-containing organisms iNOS (phospho-Tyr151) antibody (e.g., shellfish) Protection against: Bacterial infections Allergic disease Promote apoptotic cell clearance May modulate fungal infections Sialyl-lacto-N-tetraoseMammalian: Human breast milk Bacterial: type 1b Fungal/Yeast: Aspergillus fumigatus Candida albicans Protection against: Bacterial infections Invasive fungal infections May modulate: Allergic disease -1,3-glucanMammalian: None to date Bacterial: biofilms Select (German cockroach) Protection against: Some invasive fungal diseases Allergic disease May modulate: Biofilm formation Open in a separate window Introduction Glycans, polymers of glycosidically linked sugars, are one of the most basic cellular components, and exist as carbohydrate-only entities as well as covalently attached modifications of proteins (glycoproteins) or lipids (glycolipids). Here, we use glycan to indicate both oligosaccharides and polysaccharides. In mammals, glycans have diverse functions, such as marking apoptotic cells for clearance, immune self/non-self discrimination, cell-cell communication, and intracellular signaling (1, 2). Glycosylation defects in humans are linked to disease (3), and the expressed glycome can be altered during AG1295 inflammation, cellular stress, as well as malignancy (4). Even though combinatorial composition of a saccharide array can generate an enormous number of structures, the composition of mammalian glycans is usually well-conserved (5). Some microbial pathogens including bacteria, fungi, and protozoans display mammalian-associated glycans on their surfaces as an evolutionary adaptation to evade detection by the hosts immune system (6). This house can also directly contribute to pathogenicity of these organisms (7, 8). Additionally, expression of host-similar glycans by allergens may promote their engagement of innate receptors expressed by antigen-presenting cells (APCs) and epithelial cells in the lung (9, 10). In mammals, B cells and antibodies that react with self glycans exist naturally and function to promote homeostasis (11) by facilitating the clearance of dangerous and potentially inflammatory components, such as apoptotic cells (12), senescent reddish blood cells (13), and metabolic products such as oxidized lipids (14). Aside from these homeostatic functions, naturally occurring antibodies specific for mammalian glycoproteins or glycolipids identify these structures when displayed by microorganisms as well as allergens, and can facilitate their clearance (10, 12, 15, 16). Many cellular processes such as engagement of SiglecG/CD22 (17), sequestration of autoreactive antigens (12), and induction of cellular anergy (18) exist to regulate and maintain autoreactive B cells within the B cell repertoire. In this review, we discuss the expression and interactions of B cells with selected glycan epitopes that are expressed on host cells, microbes, and allergens. These epitopes include N-acetylglucosamine (GlcNAc), sialyl-lacto-N-tetraose, and -1,3-glucan. We then give some examples of how antibodies to these glycans mediate housekeeping functions and provide protection against AG1295 pathogens and allergens (Physique 1, Table 1). Antibodies to Glycans, Implications for Polyreactivity, and Infection-Induced Autoimmunity Much has been written regarding antibodies with considerable polyreactivity (19C21). The term has generally been used to describe antibody reactivity with seemingly structurally unrelated antigen targets and has been attributed to both germline and somatically mutated gene-encoded contributions to their antigen-binding sites (22, AG1295 23). The polyreactive nature of some antibodies has often been characterized by antibody binding to recombinant antigens or mimotopes in solid-phase ELISA-type assays or by western blotting of denatured complexes from microbes, mammalian tissues, or cell extracts. These assays may also AG1295 detect low-avidity binding of antibodies against neoepitopes.