The human body is challenged with constantly surveying and managing microbial guests, while preventing infection and colonization by pathogenic microbes. Both of these goals require the accurate assessment of a cell’s origin, and the ability to effect a function. Virtually all cells are covered in the coat of carbohydrates. Cell surface glycans could serve as cell identification codes when recognized by lectins. Interestingly, the carbohydrates utilized in the assembly of microbial cell surface glycans differ substantially from those found on mammalian cells. My thesis work has taken an interdisciplinary approach using protein biochemistry, chemical biology, microbiology, and immunology to study both the biosynthesis of microbial glycans and the recognition of microbial glycans by the human lectin intelectin-1 (hIntL-1). Using protein biochemistry and chemical biology I characterized the enzyme responsible for uridine 5’–diphosphate–α-D-galactofuranose (UDP-Galf) biosynthesis, UDP-galactopyranose mutase (UGM), in the nematode Caenorhabditis elegans. These studies revealed conservation between the structure and mechanism of prokaryotic and eukaryotic UGM enzymes despite significant sequence divergence (Chapter 2). While exploring the biological function of Galf–containing glycans, I became interested in how the human immune system may interact with microbe specific carbohydrates. Focusing our efforts on hIntL-1, a soluble lectin proposed to function in innate immunity, we identified several microbe specific carbohydrate ligands of the lectin that include β-D-Galf–, D-phospho-glycerol–, heptose–, D-glycero-D-talo-oct-2-ulosonic acid (KO)–, and 3-deoxy-D-manno-oct−2-ulosonic acid (KDO)–containing glycans (Chapter 3). These microbial carbohydrate residues all share an exocyclic 1,2-diol epitope that is recognized by hIntL-1. Recognition of the exocyclic diol by a Xenopus laevis intelectin suggests that intelectin:diol binding may be a general mechanism for microbe detection by chordates (Chapter 4). Lastly, hIntL-1 binding to microbial communities representative of human gastrointestinal microbiomes suggests that exocyclic 1,2-diols are abundantly present on microbial symbionts and hIntL-1 interacts judiciously and tunably with binding species present within communities (Chapter 5). I anticipate future work will reveal a role for intelectin in recognition and regulation of microbial guests at mucosal surfaces.