Trypanosoma cruzi extracellular amastigotes and host cell signaling: more pieces to the puzzle

Ferreira, Éden Ramalho; Bonfim-Melo, Alexis; Mortara, Renato Arruda; Bahia, Diana

doi:10.3389/fimmu.2012.00363

Cited by 28 publications

(28 citation statements)

References 38 publications

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“…cruzi presents to mammalian cells with three different infective forms: metacyclic trypomastigotes, bloodstream trypomastigotes and EAs. Many studies have shown that metacyclic and bloodstream trypomastigotes as well as EAs possess distinct mechanisms for host cell invasion (Mortara et al, 2005;Ferreira et al, 2012). EAs display actin-dependent invasion in non-phagocytic cells similar to phagocytosis-driven professional phagocytes (Fernandes et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…EAs display actin-dependent invasion in non-phagocytic cells similar to phagocytosis-driven professional phagocytes (Fernandes et al, 2013). Despite these observations, detailed molecular mechanisms, including involvement of regulatory proteins, are still unknown (Ferreira et al, 2012). We evaluated the role of the host actin regulating protein cortactin and one of its kinases, PKD1.…”

Section: Discussionmentioning

confidence: 99%

“…We recently showed that EA internalization by non-phagocytic cells involves specific, sequential recruitment of phosphatidylinositol phosphate markers, suggesting that the parasites trigger phagocytosis-like machinery in nonphagocytic cells (Fernandes et al, 2013). To date, involvement of host cell kinases in T. cruzi cell invasion has been evaluated mostly by analyzing inhibitor effects (Procópio et al, 1998;Fernandes et al, 2006;Magdesian et al, 2007), and the details regarding actin-dependent EA host cell invasion signalling pathways are still poorly understood (Ferreira et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Trypanosoma cruziextracellular amastigotes trigger the protein kinase D1-cortactin-actin pathway during cell invasion

Bonfim-Melo

Zanetti

Ferreira

et al. 2015

Cellular Microbiology

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Trypanosoma cruzi extracellular amastigotes (EAs) display unique mechanisms for cell invasion that are highly dependent on host actin filaments. Protein kinase D1 (PKD1) phosphorylates and modulates the activity of cortactin, a key regulator of actin dynamics. We evaluated the role of host cortactin and PKD1 in actin filament dynamics during HeLa cell invasion by EAs. Host cortactin, PKD1 and actin are recruited by EAs based on experiments in fixed and live cells by time lapse confocal microscopy. EAs trigger PKD1 and extracellular signal-regulated kinase 1/2 activation, but not Src family kinases, and selectively phosphorylate cortactin. Heat-killed EAs and non-infective epimastigotes both triggered distinct host responses and did not recruit the molecules studied herein. EA invasion was influenced by depletion or overexpression of host cortactin and PKD1, respectively, suggesting the involvement of both proteins in this event. Collectively, these results show new host cell mechanisms subverted during EA internalization into non-phagocytic cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Trypanosoma cruziextracellular amastigotes trigger the protein kinase D1-cortactin-actin pathway during cell invasion

Bonfim-Melo

Zanetti

Ferreira

et al. 2015

Cellular Microbiology

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“…Leishmania spp. promastigotes and amastigotes preferentially infect phagocytic cells of vertebrates, while T. cruzi metacyclic trypomastigotes, blood trypomastigotes and amastigotes are able to infect both phagocytic and non-phagocytic cells ( Tanowitz et al, 1992 ; Alexander et al, 1999 ; Ferreira et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

The Mitogen-Activated Protein Kinase (MAPK) Pathway: Role in Immune Evasion by Trypanosomatids

et al. 2016

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Leishmania spp. and Trypanosoma cruzi are the causative agents of leishmaniasis and Chagas disease, respectively, two neglected tropical diseases that affect about 25 million people worldwide. These parasites belong to the family Trypanosomatidae, and are both obligate intracellular parasites that manipulate host signaling pathways and the innate immune system to establish infection. Mitogen-activated protein kinases (MAPKs) are serine and threonine protein kinases that are highly conserved in eukaryotes, and are involved in signal transduction pathways that modulate physiological and pathophysiological cell responses. This mini-review highlights existing knowledge concerning the mechanisms that Leishmania spp. and T. cruzi have evolved to target the host’s MAPK signaling pathways and highjack the immune response, and, in this manner, promote parasite maintenance in the host.

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“…After penetration into the cytoplasm of the host cell, the morphology of the metacyclic trypomastigotes changes to intracellular amastigotes with diameters of 3-5 µm, when they lose their undulating membrane which is a characteristic feature of mobile trypomastigotes [9,12] (Figure 4). Intracellular amastigotes undergo several rounds of division and are then transformed into trypomastigotes, approximately 20-µm long, which leave the host cell and spread further into the organism to infect new host cells [13]. Unlike the African sleeping sickness caused by T.…”

Section: Biology and Life Cycle Of T Cruzimentioning

confidence: 99%

Novel Insights into the Pathophysiology of Chagas' Cardiomyopathy

Stahl¹,

Meyer²

2017

Cardiomyopathies - Types and Treatments

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The protozoan hemoflagellate Trypanosoma cruzi (T. cruzi) is the etiologic agent of the zoonotic Chagas' disease that affects approximately six to seven million people in Central and South America, causing dilated cardiomyopathy and megavisceral disease. Although Chagas' disease is the leading cause of heart failure in Latin America among people living in poverty and places an immense socioeconomic burden on society, it is still currently classified as a neglected tropical disease (NTD). The disease is typically transmitted by reduviid bugs or orally by contaminated food, while the transmission of parasitic organisms by other routes such as blood transfusion, organ transplantation, and transplacental infection is relatively rare. Given the wide cellular tropism infecting virtually all nucleated cells, the protozoan is able to persist asymptomatically for decades until ultimately causing organ-specific symptoms of chronic Chagas' disease such as chronic heart failure. The acute phase of the disease triggers an immune response that often does not restrict the dissemination of the parasite and may cause skin lesions, fever, enlarged lymph nodes, pallor, swelling, and abdominal and chest pain. Despite recent advances in our knowledge about the pathogenesis of this disease, the complex host-parasite interactions are not completely understood and, in particular, the persistence of parasites in host cells for such a long time remains largely undefined. In this book chapter, we focus on the pathophysiology of American trypanosomiasis and emphasize the role of host-specific transcription factors executing antiparasitic immune reactions.

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Trypanosoma cruzi extracellular amastigotes and host cell signaling: more pieces to the puzzle

Cited by 28 publications

References 38 publications

Trypanosoma cruziextracellular amastigotes trigger the protein kinase D1-cortactin-actin pathway during cell invasion

Trypanosoma cruziextracellular amastigotes trigger the protein kinase D1-cortactin-actin pathway during cell invasion

The Mitogen-Activated Protein Kinase (MAPK) Pathway: Role in Immune Evasion by Trypanosomatids

Novel Insights into the Pathophysiology of Chagas' Cardiomyopathy

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