Soluble Human Lectins at the Host-Microbe Interface

Abstract

Human lectins are integral to maintaining microbial homeostasis on the skin, in the blood, and at mucosal barriers. These proteins can recognize microbial glycans and inform the host about its microbial status. In accordance with their roles, their production can vary with tissue type. They also can have unique structural and biochemical properties, and they can influence microbial colonization at sites proximal and distal to their tissue of origin. In line with their classification as innate immune proteins, soluble lectins have long been studied in the context of acute infectious disease, but only recently have we begun to appreciate their roles in maintaining commensal microbial communities (i.e., the human microbiota). This review provides an overview of soluble lectins that operate at host-microbe interfaces, their glycan recognition properties, and their roles in physiological and pathological mechanisms.

Keywords: glycans; inflammatory bowel disease; innate immunity; intelectin; lectins; microbiome.

FIGURE 1.

Soluble lectins in the human body. Concentrations of circulating lectins are listed for those that are known.

FIGURE 2.

Schematic representation of the cell surface of Gram-negative bacteria, Gram-positive bacteria, archaea, and fungi.

FIGURE 3.

Chemical structures of (A) common bacterial carbohydrates and (B) mammalian carbohydrates. (C) Examples of mammalian and microbial glycans.

FIGURE 4.

Human lectin folds by family. Calcium ions are green, and zinc is shown in gray. Collectins: MBL (PDB 1HUP (33)) and SP-D (PDB 3DBZ (34)). Trefoil factors: TFF1 (PDB 6V1D (30)) and TFF3 (PDB 6V1C (30)). Reg proteins: RegIα (PDB 1LIT (35)), RegIIIα (PDB 1UV0 (36)), and RegIV (PDB 2KV3 (37)). Galectins: Galectin-1 (PDB 1GZW (38)), Galectin-2 (PDB 5DG2 (39)), Galectin-3 (PDB 3ZSJ (40)), Galectin-4 (PDB 4YM3 (41)), Galectin-7 (PDB 1BKZ (42)), Galectin-8 (PDB 3AP6 (43)), Galectin-9 (PDB 2EAL (44)), Galectin 10 (PDB 6L6A (45)), and Galectin 16 (PDB 6ILQ (46)). Pentraxins: CRP (PDB 1GNH (47)), SAP (PDB 3KQR (48)), and PTX3 (PDB 7ZL1 (49)). Ficolins: H-Ficolin (PDB 2J64 (29)), L-Ficolin (PDB 2J3G (29)), and M-Ficolin (PDB 2D39 (50)). X-type lectins: hItln-1 (PDB 4WMQ (32)). Zymogen granules: ZG16b (PDB 3AQG (31)) and ZG16p (PDB 3APA (31)).

FIGURE 5.

(Left) Protein structure of the C-type lectin SP-D coordinating carbohydrate hydroxyl groups the calcium in the binding pocket (green) (PDB 5OXR (56)). This represents one of two binding modes of SP-D to mannose. (Right) Protein structure of galectin-3 binding to lactose using CH-π interactions between W181 in the binding pocket (PDB 3ZSJ (40)).

FIGURE 6.

Oligomerization states of soluble lectins. Each oval represents a single CRD. For the tandem-repeat galectins, two colors are used to indicate different CRDs.

FIGURE 7.

The multiple roles soluble lectins (maroon) serve at mucosal barriers.

FIGURE 8.

(A) Glycan array schematic. Fluorescently tagged lectins are screened against a library of synthetic and natural glycans immobilized to glass slides. (B) Lectin array schematic. Lectins are attached to the arrays, and the binding of fluorescently labeled proteins or cells is assessed.