Acceptive Immunity: The Role of Fucosylated Glycans in Human Host-Microbiome Interactions

Abstract

The growth in the number of chronic non-communicable diseases in the second half of the past century and in the first two decades of the new century is largely due to the disruption of the relationship between the human body and its symbiotic microbiota, and not pathogens. The interaction of the human immune system with symbionts is not accompanied by inflammation, but is a physiological norm. This is achieved via microbiota control by the immune system through a complex balance of pro-inflammatory and suppressive responses, and only a disturbance of this balance can trigger pathophysiological mechanisms. This review discusses the establishment of homeostatic relationships during immune system development and intestinal bacterial colonization through the interaction of milk glycans, mucins, and secretory immunoglobulins. In particular, the role of fucose and fucosylated glycans in the mechanism of interactions between host epithelial and immune cells is discussed.

Keywords: acceptive immunity; fucose; fucosylated glycans; host–microbiome interactions; immune tolerance; intestinal microbiota.

Figure 1

Fucosylated glycoconjugates (A) and some human milk oligosaccharides (B), which may act as unique carbohydrate patterns. Fuc: L-fucose. Gal: galactose. Glc: glucose. GlcNAc: N-acetyl-D-glucosamine. Le^a: Lewis a antigen. Le^b: Lewis b antigen. Le^x: Lewis x antigen. Le^y: Lewis y antigen. H type 1: H antigen type 1. H type 2: H antigen type 2. 2′-FL: 2′-fucosyllactose. 3′-FL: 3′-fucosyllactose. LNFP III: lacto-N-fucopentaose III.

Figure 2

The formation of a ‘layered’ immunity in an infant through a number of sequential processes associated with fucosylation. These processes have several critical time periods, called windows of opportunity, during which the immune system is trained by antigens presented to it. The presentation of fucosylated patterns of food (oligosaccharides and glycoconjugates of breast milk) and bacterial antigens (Bacteroides) for the development of immune tolerance to them probably occurs before the opening of the second window of opportunity in the development of the immune system during breastfeeding. The synthesis of carbohydrate patterns in bacteria is determined by the type of glycans available for metabolism by intestinal bacteria. The introduction of solid foods in infancy opens a second window of opportunity due to the presentation of new food and bacterial antigens. Glycan-degrading Bacteroides stimulate the growth of Firmicutes and butyrate production, which, along with segmented filamentous bacteria (SFB), enhances the fucosylation of the intestinal epithelial glycocalyx. Human breast milk, mucin, and secretory immunoglobulin glycans are part of the host’s mechanism controlling bacterial colonization. IECs: intestinal epithelial cells. sIgs: secretory immunoglobulins.