Cell signaling during Trypanosoma cruzi invasion

Abstract

Cell signaling is an essential requirement for mammalian cell invasion by Trypanosoma cruzi. Depending on the parasite strain and the parasite developmental form, distinct signaling pathways may be induced. In this short review, we focus on the data coming from studies with metacyclic trypomastigotes (MT) generated in vitro and tissue culture-derived trypomastigotes (TCT), used as counterparts of insect-borne and bloodstream parasites, respectively. During invasion of host cells by MT or TCT, intracellular Ca2+ mobilization and host cell lysosomal exocytosis are triggered. Invasion mediated by MT surface molecule gp82 requires the activation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and protein kinase C (PKC) in the host cell, associated with Ca2+-dependent disruption of the actin cytoskeleton. In MT, protein tyrosine kinase, PI3K, phospholipase C, and PKC appear to be activated. TCT invasion, on the other hand, does not rely on mTOR activation, rather on target cell PI3K, and may involve the host cell autophagy for parasite internalization. Enzymes, such as oligopeptidase B and the major T. cruzi cysteine proteinase cruzipain, have been shown to generate molecules that induce target cell Ca2+ signal. In addition, TCT may trigger host cell responses mediated by transforming growth factor β receptor or integrin family member. Further investigations are needed for a more complete and detailed picture of T. cruzi invasion.

Who's really in control: microbial regulation of protein trafficking in the epithelium

“…In the lysosome-dependent pathway, T. cruzi engages host cells and phospholipase C is subsequently activated, which promotes production of diacylglycerol and inositol 1,4,5-tripohsphate. The initial interactions between T. cruzi and host cells seem to be a dynamic process that involves multiple T. cruzi surface molecules and/or secreted factors, depending on the lineage and system studied (11,57,101). Inositol 1,4,5-tripohsphate promotes release of Ca 2ϩ from the endoplasmic reticulum, and the increase in intracellular Ca 2ϩ promotes lysosome recruitment to the site of parasite internalization, as reviewed extensively elsewhere (57).…”

Experimental Chagas disease in Balb/c mice previously vaccinated with T. rangeli. II. The innate immune response shows immunological memory: Reality or fiction?

“…This allows the destruction of this vacuole containing the parasite, which makes it possible for the parasite to escape later into the cytoplasm (Barrias et al, 2013). Although several studies have been conducted in the field of pathogen and host cell interaction, the mechanisms involved, in recruitment and internalization, are not altogether clear (Maeda et al, 2012). It is therefore necessary to develop tools that provide better information about the biology of the parasite and its innmmune response with a view to developing new strategies for the prevention of this infection.…”

Interação parasita-célula hospedeira: modificação de proteínas de Tripanosoma cruzi durante adesão à matriz extracelular

“…Apesar do grande avanço no entendimento do processo de infecção durante os mais de 100 anos após a descoberta da doença de Chagas, os mecanismos desencadeados no parasita durante a adesão à célula hospedeira ou à matriz extracelular são ainda pouco compreendidos (revisto em Alves & Mortara, 2010, Maeda, et al, 2012. Nosso laboratório e outros vem se empenhando em identificar as vias de sinalização desencadeadas em tripomastigotas de T. cruzi durante seu contato com o hospedeiro, como a ligação entre glicoproteínas de superfamília gp85/trans-sialidase (TS) e elementos da matriz extracelular (ECM), tais como fibronectina, laminina e galectina, cruciais para a modulação da adesão e invasão do parasita.…”

“…A complexidade dos eventos é acentuada, pelas diferenças existentes entre as cepas e as formas infectivas do parasita (tripomastigota metacíclica ou sanguícola) devido ao seu repertório de moléculas e pela capacidade do parasita de invadir praticamente todas as células in vitro e in vivo, embora posteriormente no mamífero sua detecção se restrinja a alguns órgãos, (revisado por Maeda, et al, 2012).…”