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Review on Trypanosoma cruzi: Host Cell Interaction.

de Souza W, de Carvalho TM, Barrias ES - Int J Cell Biol (2010)

Bottom Line: Metacyclic trypomastigotes are released with the feces of the insect while amastigotes and bloodstream trypomastigotes are released from the infected host cells of the vertebrate host after a complex intracellular life cycle.The recognition between parasite and mammalian host cell involves numerous molecules present in both cell types.Here, we present a brief review of the interaction between Trypanosoma cruzi and its host cells, mainly emphasizing the mechanisms and molecules that participate in the T. cruzi invasion process of the mammalian cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, CCS, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Bloco G, Ilha do Fundão, RJ 21941-902, Brazil.

ABSTRACT
Trypanosoma cruzi, the causative agent of Chagas' disease, which affects a large number of individuals in Central and South America, is transmitted to vertebrate hosts by blood-sucking insects. This protozoan is an obligate intracellular parasite. The infective forms of the parasite are metacyclic and bloodstream trypomastigote and amastigote. Metacyclic trypomastigotes are released with the feces of the insect while amastigotes and bloodstream trypomastigotes are released from the infected host cells of the vertebrate host after a complex intracellular life cycle. The recognition between parasite and mammalian host cell involves numerous molecules present in both cell types. Here, we present a brief review of the interaction between Trypanosoma cruzi and its host cells, mainly emphasizing the mechanisms and molecules that participate in the T. cruzi invasion process of the mammalian cells.

No MeSH data available.


Related in: MedlinePlus

Trypomastigote vacuole is enriched in AKT-PH-GFP that binds to posphatidylinositolbiphosphate (PtdIns(3,4)P2) and phosphatidylinositoltriphosphate (PtdIns(3,4,5)P3) that are products of PI3 Kinase (a–c) and also labeled to EEA1 and Rab 5 (d–f) and Lamp-1 (g–i). (a–c) rapid accumulation of PtdIns(3,4,5)P3/PtdIns (3,4)P2 at the T. cruzi invasion site. Fluorescence images of (a) CHO cells or (b) primary rat cardiomyocytes transiently expressing Akt-PH-GFP following incubation with infective T. cruzi trypomastigotes for 15 minutes. (c) T. cruzi invasion of CHO cells expressing Akt-PH-GFPR25C which fails to bind to PtdIns (3,4,5)P3/PtdIns(3,4)P2. (d)–(f): early association of T. cruzi with early endosomes is minimal and precedes lamp-1 acquisition. Immunofluorescence staining of extracellular T. cruzi (arrowheads) following infection of CHO cells transiently expressing Rab5-GFP (green). Host cell and parasite DNA is visualized with DAPI (blue). (g–i) lamp-1 association with the Akt-PH-GFP-enriched T. cruzi vacuole occurs after parasite entry. L6E9 myoblasts expressing Akt-PH-GFP (green) were infected with T. cruzi for 60 minutes and stained with anti-lamp-1 (red) and DAPI (blue). Bars = 5 μm (after [28]).
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fig7: Trypomastigote vacuole is enriched in AKT-PH-GFP that binds to posphatidylinositolbiphosphate (PtdIns(3,4)P2) and phosphatidylinositoltriphosphate (PtdIns(3,4,5)P3) that are products of PI3 Kinase (a–c) and also labeled to EEA1 and Rab 5 (d–f) and Lamp-1 (g–i). (a–c) rapid accumulation of PtdIns(3,4,5)P3/PtdIns (3,4)P2 at the T. cruzi invasion site. Fluorescence images of (a) CHO cells or (b) primary rat cardiomyocytes transiently expressing Akt-PH-GFP following incubation with infective T. cruzi trypomastigotes for 15 minutes. (c) T. cruzi invasion of CHO cells expressing Akt-PH-GFPR25C which fails to bind to PtdIns (3,4,5)P3/PtdIns(3,4)P2. (d)–(f): early association of T. cruzi with early endosomes is minimal and precedes lamp-1 acquisition. Immunofluorescence staining of extracellular T. cruzi (arrowheads) following infection of CHO cells transiently expressing Rab5-GFP (green). Host cell and parasite DNA is visualized with DAPI (blue). (g–i) lamp-1 association with the Akt-PH-GFP-enriched T. cruzi vacuole occurs after parasite entry. L6E9 myoblasts expressing Akt-PH-GFP (green) were infected with T. cruzi for 60 minutes and stained with anti-lamp-1 (red) and DAPI (blue). Bars = 5 μm (after [28]).

Mentions: In 1987, De Carvalho and De Souza [102] showed that opsonized trypomastigote and epimastigote stages interacting with macrophages activate NAD(P)H oxidase at the host cell membrane and that this enzyme is kept activated inside the parasitophorous vacuole (PV). The first study describing the PV membrane composition used a macrophage cell line and showed: (i) the presence of Fc receptors [103] if trypomastigotes were opsonized with anti T. cruzi antibodies; (ii) β 1 integrin and lysosomal membrane glycoproteins (lgp); and (iii) the presence of complement receptors (CR3), Fc receptors if epimastigotes were opsonized with anti-T. cruzi antibodies; β 1 integrin and lysosomal membrane glycoproteins (lgp). Using muscle cells, Barbosa and de Meirelles [77] showed with Thiéry staining that glycoconjugates were present in the parasitophorous vacuole membrane. They also used ferritin labeled RCAI to detect galactosyl residues and showed that in muscle cells these residues accumulated in the parasite adhesion region and these residues were internalized during parasite invasion [77]. In 1994, Tardieux et al. [98] and Rodríguez et al. [104] showed that lysosomes migrate early to the parasite entry site in nonphagocytic host cells, contributing with membrane during the PV formation. They pointed out, as requirements for parasite entry, the participation of microtubules and kinesin in the lysosomes migration from the perinuclear region to the cell periphery [105]. The authors also show that lysosome-membrane fusion is dependent on calcium [105]. Ochatt et al. [106] showed, using macrophages that GTP-regulated factors, but not calcium-regulated elements, were involved in an early inhibition of phagosome-lysosome fusion in T. cruzi infected macrophages. Carvalho et al. [18] using fluorescent markers showed that host cell membrane lipids, proteins and sialoglycoconjugates contribute to the membrane lining the PV, which contains epimastigotes and trypomastigotes ingested by macrophages (Figure 6). Lysosome fusion at the parasite entry site during early infection of macrophages by trypomastigotes has not been clearly shown. Using nonphagocytic GFP-Rab5 transfected cells and confocal microscopy, Wilkowsky et al. [107] demonstrated the presence of Rab5 in early PV containing T cruzi, indicating that some PV fuse first with endosome vacuoles. Woolsey et al. [28], using shortly infected nonprofessional phagocytic cells, showed that 50% or more of invading T. cruzi trypomastigotes use host cell plasma membrane during the PV formation. They suggested that this process was facilitated by the depolymerization of host cell actin microfilaments. They also showed that this vacuole is enriched in products from PI 3-kinase and negative for lysosomal markers; approximately 20% of T. cruzi containing vacuoles were positive to EEA1 and Rab 5 and approximately 20% of T cruzi containing vacuoles were positive for Lamp-1 (Figure 7). Questioning T cruzi early residence in a phagolysosome, Andrade and Andrews [108], blocked T. cruzi lysosome mediated invasion and showed that the parasites were not retained inside the host cell. They concluded that the phagolysosome fusion is essential for parasite retention inside host cells and development. Concerning the lysosome fusion at the parasite entry site, Tyler et al. [109] showed that the parasitophorous vacuole containing T. cruzi acts as a secondary microtubule organizing center. More recently, Romano et al. [110] showed that the PV containing T. cruzi is decorated by the autophagic protein LC3. This paper also pointed out some interesting observations: (i) host cell starvation or pharmacological induction of autophagy before the infection with T. cruzi significantly enhances the number of infected cells, while inhibitors of this process inhibited parasite invasion; (ii) the absence or reduction of two proteins required in the initial step of autophagosome formation (Atg5 and Beclin 1) reduces both the parasite entry and Lamp-1 association with the PV; and (iii) autolysosomes are recruited to the parasite site of entry. Fernandes et al. [100] and Barrias et al. [16] observed in the PV containing T. cruzi the presence of GM1, flotillin and caveolin 1 shortly after infection, thus suggesting the presence of microdomains in the membrane lining the T. cruzi PV. Dynamin is essential to vacuole parasitophorous formation since the blockage of its GTPasic activity by dynasore (a dynamin inhibitor) impairs the parasite internalization [29] (Figure 8).


Review on Trypanosoma cruzi: Host Cell Interaction.

de Souza W, de Carvalho TM, Barrias ES - Int J Cell Biol (2010)

Trypomastigote vacuole is enriched in AKT-PH-GFP that binds to posphatidylinositolbiphosphate (PtdIns(3,4)P2) and phosphatidylinositoltriphosphate (PtdIns(3,4,5)P3) that are products of PI3 Kinase (a–c) and also labeled to EEA1 and Rab 5 (d–f) and Lamp-1 (g–i). (a–c) rapid accumulation of PtdIns(3,4,5)P3/PtdIns (3,4)P2 at the T. cruzi invasion site. Fluorescence images of (a) CHO cells or (b) primary rat cardiomyocytes transiently expressing Akt-PH-GFP following incubation with infective T. cruzi trypomastigotes for 15 minutes. (c) T. cruzi invasion of CHO cells expressing Akt-PH-GFPR25C which fails to bind to PtdIns (3,4,5)P3/PtdIns(3,4)P2. (d)–(f): early association of T. cruzi with early endosomes is minimal and precedes lamp-1 acquisition. Immunofluorescence staining of extracellular T. cruzi (arrowheads) following infection of CHO cells transiently expressing Rab5-GFP (green). Host cell and parasite DNA is visualized with DAPI (blue). (g–i) lamp-1 association with the Akt-PH-GFP-enriched T. cruzi vacuole occurs after parasite entry. L6E9 myoblasts expressing Akt-PH-GFP (green) were infected with T. cruzi for 60 minutes and stained with anti-lamp-1 (red) and DAPI (blue). Bars = 5 μm (after [28]).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
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fig7: Trypomastigote vacuole is enriched in AKT-PH-GFP that binds to posphatidylinositolbiphosphate (PtdIns(3,4)P2) and phosphatidylinositoltriphosphate (PtdIns(3,4,5)P3) that are products of PI3 Kinase (a–c) and also labeled to EEA1 and Rab 5 (d–f) and Lamp-1 (g–i). (a–c) rapid accumulation of PtdIns(3,4,5)P3/PtdIns (3,4)P2 at the T. cruzi invasion site. Fluorescence images of (a) CHO cells or (b) primary rat cardiomyocytes transiently expressing Akt-PH-GFP following incubation with infective T. cruzi trypomastigotes for 15 minutes. (c) T. cruzi invasion of CHO cells expressing Akt-PH-GFPR25C which fails to bind to PtdIns (3,4,5)P3/PtdIns(3,4)P2. (d)–(f): early association of T. cruzi with early endosomes is minimal and precedes lamp-1 acquisition. Immunofluorescence staining of extracellular T. cruzi (arrowheads) following infection of CHO cells transiently expressing Rab5-GFP (green). Host cell and parasite DNA is visualized with DAPI (blue). (g–i) lamp-1 association with the Akt-PH-GFP-enriched T. cruzi vacuole occurs after parasite entry. L6E9 myoblasts expressing Akt-PH-GFP (green) were infected with T. cruzi for 60 minutes and stained with anti-lamp-1 (red) and DAPI (blue). Bars = 5 μm (after [28]).
Mentions: In 1987, De Carvalho and De Souza [102] showed that opsonized trypomastigote and epimastigote stages interacting with macrophages activate NAD(P)H oxidase at the host cell membrane and that this enzyme is kept activated inside the parasitophorous vacuole (PV). The first study describing the PV membrane composition used a macrophage cell line and showed: (i) the presence of Fc receptors [103] if trypomastigotes were opsonized with anti T. cruzi antibodies; (ii) β 1 integrin and lysosomal membrane glycoproteins (lgp); and (iii) the presence of complement receptors (CR3), Fc receptors if epimastigotes were opsonized with anti-T. cruzi antibodies; β 1 integrin and lysosomal membrane glycoproteins (lgp). Using muscle cells, Barbosa and de Meirelles [77] showed with Thiéry staining that glycoconjugates were present in the parasitophorous vacuole membrane. They also used ferritin labeled RCAI to detect galactosyl residues and showed that in muscle cells these residues accumulated in the parasite adhesion region and these residues were internalized during parasite invasion [77]. In 1994, Tardieux et al. [98] and Rodríguez et al. [104] showed that lysosomes migrate early to the parasite entry site in nonphagocytic host cells, contributing with membrane during the PV formation. They pointed out, as requirements for parasite entry, the participation of microtubules and kinesin in the lysosomes migration from the perinuclear region to the cell periphery [105]. The authors also show that lysosome-membrane fusion is dependent on calcium [105]. Ochatt et al. [106] showed, using macrophages that GTP-regulated factors, but not calcium-regulated elements, were involved in an early inhibition of phagosome-lysosome fusion in T. cruzi infected macrophages. Carvalho et al. [18] using fluorescent markers showed that host cell membrane lipids, proteins and sialoglycoconjugates contribute to the membrane lining the PV, which contains epimastigotes and trypomastigotes ingested by macrophages (Figure 6). Lysosome fusion at the parasite entry site during early infection of macrophages by trypomastigotes has not been clearly shown. Using nonphagocytic GFP-Rab5 transfected cells and confocal microscopy, Wilkowsky et al. [107] demonstrated the presence of Rab5 in early PV containing T cruzi, indicating that some PV fuse first with endosome vacuoles. Woolsey et al. [28], using shortly infected nonprofessional phagocytic cells, showed that 50% or more of invading T. cruzi trypomastigotes use host cell plasma membrane during the PV formation. They suggested that this process was facilitated by the depolymerization of host cell actin microfilaments. They also showed that this vacuole is enriched in products from PI 3-kinase and negative for lysosomal markers; approximately 20% of T. cruzi containing vacuoles were positive to EEA1 and Rab 5 and approximately 20% of T cruzi containing vacuoles were positive for Lamp-1 (Figure 7). Questioning T cruzi early residence in a phagolysosome, Andrade and Andrews [108], blocked T. cruzi lysosome mediated invasion and showed that the parasites were not retained inside the host cell. They concluded that the phagolysosome fusion is essential for parasite retention inside host cells and development. Concerning the lysosome fusion at the parasite entry site, Tyler et al. [109] showed that the parasitophorous vacuole containing T. cruzi acts as a secondary microtubule organizing center. More recently, Romano et al. [110] showed that the PV containing T. cruzi is decorated by the autophagic protein LC3. This paper also pointed out some interesting observations: (i) host cell starvation or pharmacological induction of autophagy before the infection with T. cruzi significantly enhances the number of infected cells, while inhibitors of this process inhibited parasite invasion; (ii) the absence or reduction of two proteins required in the initial step of autophagosome formation (Atg5 and Beclin 1) reduces both the parasite entry and Lamp-1 association with the PV; and (iii) autolysosomes are recruited to the parasite site of entry. Fernandes et al. [100] and Barrias et al. [16] observed in the PV containing T. cruzi the presence of GM1, flotillin and caveolin 1 shortly after infection, thus suggesting the presence of microdomains in the membrane lining the T. cruzi PV. Dynamin is essential to vacuole parasitophorous formation since the blockage of its GTPasic activity by dynasore (a dynamin inhibitor) impairs the parasite internalization [29] (Figure 8).

Bottom Line: Metacyclic trypomastigotes are released with the feces of the insect while amastigotes and bloodstream trypomastigotes are released from the infected host cells of the vertebrate host after a complex intracellular life cycle.The recognition between parasite and mammalian host cell involves numerous molecules present in both cell types.Here, we present a brief review of the interaction between Trypanosoma cruzi and its host cells, mainly emphasizing the mechanisms and molecules that participate in the T. cruzi invasion process of the mammalian cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, CCS, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Bloco G, Ilha do Fundão, RJ 21941-902, Brazil.

ABSTRACT
Trypanosoma cruzi, the causative agent of Chagas' disease, which affects a large number of individuals in Central and South America, is transmitted to vertebrate hosts by blood-sucking insects. This protozoan is an obligate intracellular parasite. The infective forms of the parasite are metacyclic and bloodstream trypomastigote and amastigote. Metacyclic trypomastigotes are released with the feces of the insect while amastigotes and bloodstream trypomastigotes are released from the infected host cells of the vertebrate host after a complex intracellular life cycle. The recognition between parasite and mammalian host cell involves numerous molecules present in both cell types. Here, we present a brief review of the interaction between Trypanosoma cruzi and its host cells, mainly emphasizing the mechanisms and molecules that participate in the T. cruzi invasion process of the mammalian cells.

No MeSH data available.


Related in: MedlinePlus