Trypanosoma cruzi: Shedding of surface antigens as membrane vesicles

Goncalves, M F; Umezawa, Eufrosina Setsu; Katzin, Alejandro M.; Souza, Wanderley de; Alves, Maria Júlia Manso; Zingales, Bianca; Colli, Walter

doi:10.1016/0014-4894(91)90119-h

Cited by 142 publications

(121 citation statements)

References 29 publications

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“…The knowledge of the intimate mechanism of surface antigen shedding would contribute to the understanding of these phenomena. In this direction we have already described the shedding of lipidic components to the culture medium of the infective forms (Couto et al 1991), supporting reports for the spontaneous release of antigens in vesicles (Gonçalves et al 1991).…”

Section: Discussionsupporting

confidence: 81%

“…We have already characterized neutral and zwitterionic lipids (Uhrig et al 1997) and inositolphospholipids (Uhrig et al 1996), among others (Couto et al 1985, Uhrig et al 1992. The shedding of different lipidic components in vesicles has been reported (Gonçalves et al 1991). Qualitative and quantitative differences between the shed components and the lipids remaining in the parasite were observed (Couto et al 1991 Lipid extraction -Parasites and the corresponding dried medium were twice extracted with chloroform:methanol 2:1 and 1:1 (v/v).…”

Section: Parasites -Trypomastigotes Of T Cruzimentioning

confidence: 99%

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Lipids shed into the culture medium by trypomastigotes of Trypanosoma cruzi

Agusti

Couto

Alves

et al. 2000

Mem. Inst. Oswaldo Cruz

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Section: Discussionsupporting

confidence: 81%

Section: Parasites -Trypomastigotes Of T Cruzimentioning

confidence: 99%

Lipids shed into the culture medium by trypomastigotes of Trypanosoma cruzi

Agusti

Couto

Alves

et al. 2000

Mem. Inst. Oswaldo Cruz

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“…In addition, circulating antibodies directed against these hypervariable regions were detected in T. cruzi infected humans and animals (28), 4 suggesting that these sequences are indeed exposed to the mammalian immune system. One interesting possibility is that TcMUC I products are expressed by the mammal-dwelling stages, but are barely detected because they are prone to massive shedding to the medium either by cleavage of their GPI anchor (28) or by their differential partition into released vesicles (44) or membrane-bound trails (45). Further studies are required to address the expression pattern of Tc-MUC I products and to clarify the in vivo biological function and immunological implications of TcMUC II diversity.…”

Section: Fig 3 Stage Expression Of Tcmuc II Productsmentioning

confidence: 99%

The Surface Coat of the Mammal-dwelling Infective Trypomastigote Stage of Trypanosoma cruzi Is Formed by Highly Diverse Immunogenic Mucins

Buscaglia

Campo

Noia

et al. 2004

Journal of Biological Chemistry

107

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A thick coat of mucin-like glycoproteins covers the surface of Trypanosoma cruzi and plays a crucial role in parasite protection and infectivity and host immunomodulation. The appealing candidate genes coding for the mucins of the mammal-dwelling stages define a heterogeneous family termed TcMUC, which comprises up to 700 members, thus precluding a genetic approach to address the protein core identity. Here, we demonstrate by multiple approaches that the TcMUC II genes code for the majority of trypomastigote mucins. These molecules display a variable, non-repetitive, highly O-glycosylated central domain, followed by a short conserved C terminus and a glycosylphosphatidylinositol anchor. A simultaneous expression of multiple TcMUC II gene products was observed. Moreover, the C terminus of TcMUC II mucins, but not their central domain, elicited strong antibody responses in patients with Chagas' disease and T. crusi infected animals. This highly diverse coat of mucins may represent a refined parasite strategy to elude the mammalian host immune system.Trypanosoma cruzi is the etiologic agent of Chagas' disease, which is of major medical and economical significance in Latin America (1). The T. cruzi life cycle involves distinct stages in both the mammalian host and the hematophagous insect vector (2). Within the insect, two major developmental forms can be observed: replicative epimastigotes and metacyclic trypomastigotes. The latter form brings the infection into humans when released on the skin or mucosa after the insect blood meal. Following cell invasion, metacyclic trypomastigotes differentiate into amastigotes, which, after several divisions, transform into cell-derived trypomastigotes, which are then released into the bloodstream. This stage is able to invade a wide variety of nucleated cells, thus propagating the infection.A thick coat of glycoproteins covers the surface of all these developmental stages (3-11). The major protein components of this coat have been identified as glycosylphosphatidylinositol (GPI) 1 -anchored molecules enriched in Thr, Ser, and Pro residues that serve as a scaffold for the extensive addition of O-glycans (5, 8 -10, 12). This particular feature enables their classification as mucin-like proteins by analogy to mammalian mucins (13). Mucins play a key role in parasite protection and infectivity and modulation of the host immune response throughout the T. cruzi life cycle (14 -16). The mucin coat of the cell-derived trypomastigotes (tGPI-mucins) is composed of an undefined mixture of molecules ranging from 60 to 220 kDa (6, 7, 9) and sharing the stage-specific, sialic acid-containing epitope Ssp-3, critical for mammalian cell attachment/invasion (17, 18). tGPI-mucins or their GPI moieties are potent inducers of nitric oxide and pro-inflammatory cytokines by macrophages (15,19). Major protective lytic antibodies directed against ␣-galactosyl epitopes present in tGPI-mucins have been described in sera from chronic Chagas' disease patients (6, 7, 9, 11).Recently, substantial informatio...

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“…Subsequently, Gonçalves, et al [45] showed release of 20-80 nm vesicles resembling what is now known as exosomes along the entire extent of tissue culture-derived trypomastigotes. Vesicles with these dimensions can be observed by Scanning Electron Microscopy (SEM) at the infection moment ( Figure 4).…”

Section: Exosomes In the Protozoan Trypanosoma Cruzimentioning

confidence: 99%

Exosomes in the Pathogenic Protozoan Trypanosoma Cruzi

Souza¹

2017

Int J Pathol Clin Res

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Significant advances have recently occurred in the identification and characterization of different types of microvesicles released by eukaryotic cells into the extracellular space. Exosomes are one such type of these vesicles they originate from multivesicular bodies and have received much attention. Here, we review the available data on microvesicles secreted by the pathogenic protozoan Trypanosoma cruzi, which is the causative agent of Chagas disease and that still has a high prevalence in Latin America. The available data show that T. cruzi exosomes contain some key proteins and RNA molecules that contain genetic information and may interfere with transcription. The available information suggests that they play some role in the biology of T. cruzi, including its interaction with host cells, as well as on the pathogenesis of Chagas disease where inflammatory processes and host cell dead occurs as a consequence of parasites, factors released by the parasites, and molecules produced by different host cells that are part of the immunological response.

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Trypanosoma cruzi: Shedding of surface antigens as membrane vesicles

Cited by 142 publications

References 29 publications

Lipids shed into the culture medium by trypomastigotes of Trypanosoma cruzi

Lipids shed into the culture medium by trypomastigotes of Trypanosoma cruzi

The Surface Coat of the Mammal-dwelling Infective Trypomastigote Stage of Trypanosoma cruzi Is Formed by Highly Diverse Immunogenic Mucins

Exosomes in the Pathogenic Protozoan Trypanosoma Cruzi

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