The Blessed Union of Glycobiology and Immunology: A Marriage That Worked.

In this article, we discuss the main aspects regarding the recognition of cell surface glycoconjugates and the immunomodulation of responses against the progression of certain pathologies, such as cancer and infectious diseases. In the first part, we talk about different aspects of glycoconjugates and delve deeper into the importance of N-glycans in cancer immunotherapy. Then, we describe two important lectin families that have been very well studied in the last 20 years. Examples include the sialic acid-binding immunoglobulin (Ig)-like lectins (siglecs), and galectins. Finally, we discuss a topic that needs to be better addressed in the field of glycoimmunology: the impact of oncofetal antigens on the cells of the immune system. New findings in this area are of great importance for advancement, especially in the field of oncology, since it is already known that cellular interactions mediated by carbohydrate-carbohydrate and/or carbohydrate proteins are able to modulate the progression of different types of cancer in events that compromise the functionality of the immune responses.

Expression of O-glycosylated oncofetal fibronectin in alternatively activated human macrophages.

Macrophage (Mϕ) polarization is an essential phenomenon for the maintenance of homeostasis and tissue repair, and represents the event by which Mϕ reach divergent functional phenotypes as a result to specific stimuli and/or microenvironmental signals. Mϕ can be polarized into two main phenotypes, M1 or classically activated and M2 or alternatively activated. These two categories diverge in many aspects, such as secreted cytokines, markers of cell surface, and biological functions. Over the last 10 years, many potential markers have been proposed for both M1 and M2 human Mϕ. However, there is scarce information regarding the glycophenotype adopted by these cells. Here, we show that M2- but not M1-polarized Mϕ expresses high levels of an unusual glycoform of fibronectin (FN), named O-glycosylated oncofetal FN (onf-FN), found in fetal/cancer cells, but not in healthy tissues. The onf-FN expression was confirmed in vitro by Western blot and real-time RT-qPCR in primary and cell line monocyte-derived Mϕ. onf-FN was induced by IL-4 and IL-13, but not by pro-inflammatory stimuli (LPS and INF-γ). RNA and protein analysis clearly demonstrated that it is specifically associated with the M2 polarization. In conclusion, we show by the first time that O-glycosylated onf-FN is expressed by M2-polarized Mϕ.

Glycobiology of Cancer: Sugar Drives the Show.

Cancer development and progression is associated with aberrant changes in cellular glycosylation. Cells expressing altered glycan-structures are recognized by cells of the immune system, favoring the induction of inhibitory immune processes which subsequently promote tumor growth and spreading. Here, we discuss about the importance of glycobiology in modern medicine, taking into account the impact of altered glycan structures expressed in cancer cells as potential glycobiomarkers of disease, as well as on cancer development and progression.

The Sweet Side of Fungal Infections: Structural Glycan Diversity and Its Importance for Pathogenic Adaptation.

Fungal infections are the most common secondary infections in debilitated individuals in a state of chronic disease or immunosuppression. Despite this, most fungal infections are neglected, mainly due to the lower frequency of their more severe clinical forms in immunocompetent individuals with a healthy background. However, over the past few years, several cases of severe fungal infections in healthy individuals have provoked a change in the epidemiological dynamics of fungal infections around the world, both due to recurrent outbreaks in previously infrequent regions and the greater emergence of more pathogenic fungal variants affecting healthy individuals, such as in the Cryptococcus genus. Therefore, before the arrival of a scenario of prevalent severe fungal infections, it is necessary to assess more carefully what are the real reasons for the increased incidence of fungal infection globally. What are the factors that are currently contributing to this new possible epidemiological dynamic? Could these be of a structural nature? Herein, we propose a discussion based on the importance of the virulence factors of glycoconjugate composition in the adaptation of pathogenic fungal species into the current scenario of increasing severity of these infections.