Abstract
The last decades have produced a plethora of evidence on the role of glycans, from cell adhesion to signaling pathways. Much of that information pertains to their role on the immune system and their importance on the surface of many human pathogens. A clear example of this is the flagellated protozoan Trypanosoma cruzi, which displays on its surface a great variety of glycoconjugates, including O-glycosylated mucin-like glycoproteins, as well as multiple glycan-binding proteins belonging to the trans-sialidase (TS) family. Among the latter, different and concurrently expressed molecules may present or not TS activity, and are accordingly known as active (aTS) and inactive (iTS) members. Over the last thirty years, it has been well described that T. cruzi is unable to synthesize sialic acid (SIA) on its own, making use of aTS to steal the host's SIA. Although iTS did not show enzymatic activity, it retains a substrate specificity similar to aTS (α-2,3 SIA-containing glycotopes), displaying lectinic properties. It is accepted that aTS members act as virulence factors in mammals coursing the acute phase of the T. cruzi infection. However, recent findings have demonstrated that iTS may also play a pathogenic role during T. cruzi infection, since it modulates events related to adhesion and invasion of the parasite into the host cells. Since both aTS and iTS proteins share structural substrate specificity, it might be plausible to speculate that iTS proteins are able to assuage and/or attenuate biological phenomena depending on the catalytic activity displayed by aTS members. Since SIA-containing glycotopes modulate the host immune system, it should not come as any surprise that changes in the sialylation of parasite's mucin-like molecules, as well as host cell glycoconjugates might disrupt critical physiological events, such as the building of effective immune responses. This review aims to discuss the importance of mucin-like glycoproteins and both aTS and iTS for T. cruzi biology, as well as to present a snapshot of how disturbances in both parasite and host cell sialoglycophenotypes may facilitate the persistence of T. cruzi in the infected mammalian host.
Highlights
Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology
A clear example of this is the flagellated protozoan Trypanosoma cruzi, which displays on its surface a great variety of glycoconjugates, including O-glycosylated mucin-like glycoproteins, as well as multiple glycan-binding proteins belonging to the trans-sialidase (TS) family
We focused on the role of T. cruzi glycoconjugates and associated proteins in mediating the relationship between parasite and the human immune system
Summary
Trypanosoma cruzi mucins are the parasite’s most abundant surface glycoproteins. First described by Alves and Colli in epimastigotes, these highly glycosylated GPI-anchored mucinlike proteins were named A, B, and C glycoproteins [71]. The T. cruzi small mucin gene (TcSMUG) family encodes proteins that are expressed in the insect stages of the parasite’s life, being essential to the infectivity on the insect host [75], while the TcMUC family, comprising from five to seven hundred genes, encodes the proteins expressed in the mammalian host These proteins contain well-conserved Nand C-terminal regions, corresponding to ER and GPI anchor signals, respectively [72, 74, 76]. TcMUCIII refers solely to the expression of a small surface protein, TSSA, or trypomastigote small surface antigen, being expressed only on cell-derived trypomastigotes [15] These mucin-like molecules contain a great number of O-linked oligosaccharides that are the main acceptors of SIA in the parasite’s surface (Figure 1) [78,79,80,81]. The authors confirmed that the desialylation of the parasite’s surface molecules prevents such event [100]
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