<i>Trypanosoma cruzi</i>parasites fight for control of the JAK-STAT pathway by disarming their host

Stahl, Philipp; Schwarz, Ralph Τ.; Debierre‐Grockiego, Françoise; Meyer, Thomas

doi:10.1080/21623996.2015.1012964

Cited by 10 publications

(6 citation statements)

References 64 publications

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“…The SOCS3 expression attenuates the macrophage's response to IFN-γ at both proximal level activation and downstream expression. Hence, taken together above-mentioned observations indicate that the potential role of leptin signaling in various pathogens has been summarized in a schematic diagram (Figure 2 ) ( 192 – 205 ). Therefore, understanding the link between nutrition, leptin, and immune dysfunction in murine and human infectious diseases will inform targeted interventions for a vulnerable population with undernutrition, which is a crucial need for new approaches to reduce global mortality from infectious diseases.…”

Section: Conclusion and Summarymentioning

confidence: 96%

Leptin Functions in Infectious Diseases

et al. 2018

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Leptin, a pleiotropic protein has long been recognized to play an important role in the regulation of energy homeostasis, metabolism, neuroendocrine function, and other physiological functions through its effects on the central nervous system (CNS) and peripheral tissues. Leptin is secreted by adipose tissue and encoded by the obese (ob) gene. Leptin acts as a central mediator which regulates immunity as well as nutrition. Importantly, leptin can modulate both innate and adaptive immune responses. Leptin deficiency/resistance is associated with dysregulation of cytokine production, increased susceptibility toward infectious diseases, autoimmune disorders, malnutrition and inflammatory responses. Malnutrition induces a state of immunodeficiency and an inclination to death from communicable diseases. Infectious diseases are the disease of poor who invariably suffer from malnutrition that could result from reduced serum leptin levels. Thus, leptin has been placed at the center of many interrelated functions in various pathogenic conditions, such as bacterial, viruses and parasitic infections. We review herein, the recent advances on the role of leptin in malnutrition in pathogenesis of infectious diseases with a particular emphasis on parasitic diseases such as Leishmaniasis, Trypanosomiasis, Amoebiasis, and Malaria.

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Section: Conclusion and Summarymentioning

confidence: 96%

Leptin Functions in Infectious Diseases

et al. 2018

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“…The activation of STAT3 in cardiomyocytes during T. cruzi infection was associated with increased expression of anti-apoptotic factors including Bcl2 to facilitate cell survival ( 70 ) facilitating T. cruzi infection and immune evasion ( 71 ). Other interleukin mediators such as IL-7, IL-8, IL-10, and IL-11 have also been suggested to induce STAT3-mediated effects to influence inflammatory responses were evaluated ( Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi Dysregulates piRNAs Computationally Predicted to Target IL-6 Signaling Molecules During Early Infection of Primary Human Cardiac Fibroblasts

et al. 2022

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Trypanosoma cruzi , the etiological agent of Chagas disease, is an intracellular protozoan parasite, which is now present in most industrialized countries. About 40% of T. cruzi infected individuals will develop severe, incurable cardiovascular, gastrointestinal, or neurological disorders. The molecular mechanisms by which T. cruzi induces cardiopathogenesis remain to be determined. Previous studies showed that increased IL-6 expression in T. cruzi patients was associated with disease severity. IL-6 signaling was suggested to induce pro-inflammatory and pro-fibrotic responses, however, the role of this pathway during early infection remains to be elucidated. We reported that T. cruzi can dysregulate the expression of host PIWI-interacting RNAs (piRNAs) during early infection. Here, we aim to evaluate the dysregulation of IL-6 signaling and the piRNAs computationally predicted to target IL-6 molecules during early T. cruzi infection of primary human cardiac fibroblasts (PHCF). Using in silico analysis, we predict that piR_004506, piR_001356, and piR_017716 target IL6 and SOCS3 genes, respectively. We validated the piRNAs and target gene expression in T. cruzi challenged PHCF. Secreted IL-6, soluble gp-130, and sIL-6R in condition media were measured using a cytokine array and western blot analysis was used to measure pathway activation. We created a network of piRNAs, target genes, and genes within one degree of biological interaction. Our analysis revealed an inverse relationship between piRNA expression and the target transcripts during early infection, denoting the IL-6 pathway targeting piRNAs can be developed as potential therapeutics to mitigate T. cruzi cardiomyopathies.

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“…Tyrosine kinase C (TrkC) is recognized by T. cruzi parasitederived neurotrophic factor (PDNF) through neurotrophin receptor culminating in the entry of trypomastigotes into cardiac cells, while TrkA activation by the same ligand in the same cell types leads to a decrease in oxidative stress [101]. In this same sense of protection from the T. cruzi infection, other signaling pathways are also activated as, for example, the pathways of Erk11/Erk2 and Jak/STATs [102]. Other protein kinases also participate in T. cruzi invasion in host cells, such as protein kinase C (PKC), MAP kinases, and phosphatidylinositol 3-kinases (PI3-K) [86,88,97].…”

Section: Signaling Pathways Involved In Trypomastigote Penetrationmentioning

confidence: 99%

How Does the Main Infective Stage ofT. cruziEnter and Avoid Degradation in Host Cells? A Description of the Pathways and Organelles Involved on These Processes

Barrias¹,

Reignault²,

Souza³

2019

Biology OfTrypanosoma Cruzi

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Trypanosoma cruzi, the etiological agent of Chagas disease, is an intracellular parasite that targets specific proteins of the host cell resulting in the generation of a unique parasitophorous vacuole (PV). As an intracellular parasite, T. cruzi interacts with cells from the mammalian host. Here we review aspects related with the binding of the main infective developmental stage (trypomastigote) to the host cell and its recognition by surface-exposed ligands/receptors. This process involves numerous signaling pathways and culminates in the entry of the parasite and modifications in both cells. The invasion of trypomastigotes occurs through multiple endocytic process, assembly of the PV, interaction of this vacuole with the endolysosomal system, lysis of the PV membrane, and multiplication of amastigotes within the cell in direct contact with host cell organelles.assumed that replicating epimastigotes present in the insect gut are not infective to mammalian host. During the vector infection (caused by a hematophagous insect of the family Reduviidae), metacyclic trypomastigotes [8], which penetrate the vertebrate host (several mammals, including man), are released along with their excreta coming in contact with conjunctiva areas or through small lesions in the own site of the bite (favored by the itch caused after the insect's bite). In turn, metacyclic trypomastigotes are able to invade virtually all cell types in the vertebrate host, especially muscle cells, fibroblasts, and macrophages [6]. At this moment, the intracellular cycle of T. cruzi begins, where the firing of several signaling cascades culminates with the closure of the parasitophorous vacuole (PV) where the parasite is found [9,10]. After the PV closure, the process of differentiation of the parasite from the trypomastigote stage to the amastigote stage begins. At the same time, fragmentation of the PV membrane takes place most probably due to the increased concentration of the Tc-Tox perforin-like protein produced by the parasite [11]. After the destruction of the vacuole, the parasite, in the process of differentiation, will be found in the cytoplasm of the host cell where it will initiate its multiplication and subsequent differentiation for trypomastigotes culminating in the rupture of the host cell (Figure 1) [13]. The whole process of formation of the parasitophorous vacuole until its rupture counts on the participation of several organelles of the host cell. Among these, the best characterized is the participation of host cell endosomes and lysosomes. It is the fusion of these organelles with the PV membrane that probably allows the increase or expansion of the PV. In addition, this process is also responsible for the generation of an acidic environment within the PV, which probably will potentiate the action of Tc-Tox and PV membrane fragmentation [13]. Wilkowsky and colleagues [14] have shown that early and late endosomes were critical for vacuole formation. In addition, other organelles responsible for the production of proteins and energy (...

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Trypanosoma cruziparasites fight for control of the JAK-STAT pathway by disarming their host

Cited by 10 publications

References 64 publications

Leptin Functions in Infectious Diseases

Leptin Functions in Infectious Diseases

Trypanosoma cruzi Dysregulates piRNAs Computationally Predicted to Target IL-6 Signaling Molecules During Early Infection of Primary Human Cardiac Fibroblasts

How Does the Main Infective Stage ofT. cruziEnter and Avoid Degradation in Host Cells? A Description of the Pathways and Organelles Involved on These Processes

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