scholarly journals Is Antibody-Dependent Enhancement of Trypanosoma cruzi Infection Contributing to Congenital/Neonatal Chagas Disease?

2021 ◽  
Vol 12 ◽  
Author(s):  
Yves Carlier ◽  
Carine Truyens ◽  
Eric Muraille
Keyword(s):  
Trypanosoma Cruzi ◽  
Pregnant Women ◽  
Chagas Disease ◽  
Viral Infections ◽  
Neonatal Morbidity ◽  
Host Cells ◽  
Antibody Dependent Enhancement ◽  
Severe Reduction ◽  
Cruzi Infection

The newborns of women infected with the parasite Trypanosoma cruzi (the agent of Chagas disease) can be infected either before birth (congenitally), or after birth (as e.g., by vector route). Congenital Chagas disease can induce high levels of neonatal morbidity and mortality. Parasite-infected pregnant women transmit antibodies to their fetus. Antibodies, by opsonizing parasites, can promote phagocytosis and killing of T. cruzi by cells expressing FcγR, on the mandatory condition that such cells are sufficiently activated in an inflammatory context. Antibody-dependent enhancement (ADE) is a mechanism well described in viral infections, by which antibodies enhance entry of infectious agents into host cells by exploiting the phagocytic FcγR pathway. Previously reported Chagas disease studies highlighted a severe reduction of the maternal-fetal/neonatal inflammatory context in parasite-transmitting pregnant women and their congenitally infected newborns. Otherwise, experimental observations brought to light ADE of T. cruzi infection (involving FcγR) in mouse pups displaying maternally transferred antibodies, out of an inflammatory context. Herein, based on such data, we discuss the previously unconsidered possibility of a role of ADE in the trans-placental parasite transmission, and/or the development of severe and mortal clinical forms of congenital/neonatal Chagas disease in newborns of T. cruzi-infected mothers.

scholarly journals SB-431542, a Transforming Growth Factor β Inhibitor, Impairs Trypanosoma cruzi Infection in Cardiomyocytes and Parasite Cycle Completion

2007 ◽  
Vol 51 (8) ◽  
pp. 2905-2910 ◽  
Author(s):  
Mariana C. Waghabi ◽  
Michelle Keramidas ◽  
Claudia M. Calvet ◽  
Marcos Meuser ◽  
Maria de Nazaré C. Soeiro ◽  
...  
Keyword(s):  
Growth Factor ◽  
Trypanosoma Cruzi ◽  
Signaling Pathway ◽  
Chagas Disease ◽  
Transforming Growth Factor ◽  
Parasitic Infection ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Cruzi Infection

ABSTRACT The antiinflammatory cytokine transforming growth factor β (TGF-β) plays an important role in Chagas disease, a parasitic infection caused by the protozoan Trypanosoma cruzi. In the present study, we show that SB-431542, an inhibitor of the TGF-β type I receptor (ALK5), inhibits T. cruzi-induced activation of the TGF-β pathway in epithelial cells and in cardiomyocytes. Further, we demonstrate that addition of SB-431542 greatly reduces cardiomyocyte invasion by T. cruzi. Finally, SB-431542 treatment significantly reduces the number of parasites per infected cell and trypomastigote differentiation and release. Taken together, these data further confirm the major role of the TGF-β signaling pathway in both T. cruzi infection and T. cruzi cell cycle completion. Our present data demonstrate that small inhibitors of the TGF-β signaling pathway might be potential pharmacological tools for the treatment of Chagas disease.

Abstract P407: Role Of Cyclic AMP During The Intracellular Infection Cycle Of Trypanosoma Cruzi

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Daniel E Velez-Ramirez ◽  
Michelle Shimogawa ◽  
Kent Hill
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Host Cells ◽  
Camp Signaling ◽  
Host Immune System ◽  
Infection Cycle ◽  
Tropical Regions ◽  
Host Environment ◽  
Intracellular Infection

Trypanosoma cruzi is the causative agent of Chagas disease, a vector-borne disease. In the 1990s the distribution of the vector, a hematophagous triatomine, and consequently the parasite, was from the southeast tropical regions of Mexico to South America. Now, global warming is causing this distribution to expand to northern territories in Mexico, reaching southern parts of US, in which up to 300,000 people are affected. Furthermore, an increase in chronically-infected immigrants to the US makes Chagas disease a matter of Pan-American public health that it should be addressed by all the America countries. Chagas disease manifests clinically as cardiovascular disease, characterized by hypertrophy of heart, esophagus and colon. Congestive heart failure is the main cause of death (58%) in Chagas patients, whereas cardiac arrhythmias and unexpected deaths add another 36%. A major cause of heart pathology in Chagas disease damage is caused by the host immune system, as it attacks chronically infected tissue. Therefore, pathology of the disease is a direct consequence of the ability of the parasite to invade host cells, so it can establish chronic infection. To achieve this, T. cruzi must sense and adapt to the host environment, but the underlying mechanisms are poorly understood. In particular, parasite signaling pathways used to sense and transduce signals from the host environment are most completely unknown. Our lab studies cAMP signaling in trypanosome parasites and several lines of evidence suggest T. cruzi cAMP signaling is important for host cell invasion, differentiation and persistent infection, which in turn underlies heart tissue pathology of Chagas disease. A transcriptome analysis revealed that mRNA of proteins involved in cAMP metabolism, i.e. adenylate cyclases and phosphodiesterases, are either upregulated or downregulated during the intracellular infection cycle. In fact, the phosphodiesterases have flagellar homologs with known cAMP signaling functions in a related parasite. This suggests that cAMP might fluctuate during as T. cruzi invades, differentiates, and multiplies inside the host cells. We have implemented a cAMP FRET sensor to monitor cAMP levels in trypanosomes to understand the role of cAMP in T. cruzi pathogenesis.

Trypanosoma cruzi infection in Latin American pregnant women living outside endemic countries and frequency of congenital transmission: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Valeria Colombo ◽  
Andrea Giacomelli ◽  
Giovanni Casazza ◽  
Laura Galimberti ◽  
Cecilia Bonazzetti ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Pregnant Women ◽  
Chagas Disease ◽  
Latin American ◽  
Transmission Rate ◽  
Congenital Infection ◽  
Health Concern ◽  
Congenital Transmission ◽  
Global Rate ◽  
Cruzi Infection

Abstract Background Chagas disease, as a consequence of globalization and immigration, is no more restricted to Central and Latin America. Therefore, congenital transmission represents a growing public health concern in non-endemic countries. Methods The aim of this study was to assess the prevalence of Trypanosoma cruzi infection in pregnant Latin American (LA) women living outside endemic countries and the rate of congenital transmission. Data were extracted from studies indexed in PubMed, Scopus, Embase, Lilacs and SciELO databases without language restriction. Two investigators independently collected data on study characteristics, diagnosis, prevalence of infection in pregnant women and congenital infection rate. The data were pooled using a random effects model. Results The search identified 1078 articles of which 29 were eligible regarding prevalence of T. cruzi infection among pregnant women and 1795 articles of which 32 were eligible regarding the congenital transmission rate. The estimated pooled prevalence of T. cruzi infection in LA pregnant women was 4.2% [95% confidence interval (CI): 3.0–5.5]. The prevalence of T. cruzi infection in pregnant women from Bolivia was 15.5% (95% CI: 11.7–19.7) and 0.5% (95% CI: 0.2–0.89) for those coming from all other LA countries. The estimated global rate of congenital transmission was 3.5% (95% CI: 2.5–4.5); excluding poor-quality studies, the rate of congenital transmission was 3.8% (95% CI: 2.4–5.1). Conclusions Prevalence of Chagas disease among LA pregnant women living outside endemic countries is high, particularly in Bolivian women. The rate of vertical transmission of T. cruzi infection is similar to the rate reported in South and Central American countries.

Kinetics of Trypanosoma cruzi infection in guinea-pigs, with special reference to the involvement of epidermal Langerhans' cells in the induction of immunity

Parasitology ◽  
2001 ◽  
Vol 123 (4) ◽  
pp. 373-380 ◽  
Author(s):  
M. NARGIS ◽  
M. M. CHISTY ◽  
Y. IHAMA ◽  
H. SATO ◽  
T. INABA ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Guinea Pigs ◽  
Langerhans Cells ◽  
Regional Lymph Node ◽  
Kinetics Of ◽  
Cruzi Infection ◽  
Epidermal Langerhans Cells

Several studies have confirmed that epidermal Langerhans' cells (LC) play a central role in the induction of skin-related immunological events. In order to assess the role of LC in Chagas' disease, guinea-pigs were infected intradermally with Trypanosoma cruzi, sacrificed at different time-points, and their tissues were processed for routine histology, electron microscopy and immunohistochemistry. Parasitaemia was observed earliest at day 6 p.i. with 2 peaks at days 9 and 28, and disappeared on day 56 p.i. Parasite-specific serum IgG and IgM were first detected on day 12 p.i. The level of IgG gradually increased by day 84 p.i. All the infected guinea-pigs showed significant alterations in the distribution and morphology of epidermal LC during parasitaemia. The number of LC had significantly decreased in the epidermis by day 3 p.i., only returning to normal levels by day 56 p.i., although the number of LC in the underlying dermis increased concomitantly. Parasites were carried to the regional lymph node, where clustering of parasite-laden dendritic cells (DC) with lymphocytes was seen by electron microscopy. This evidence suggests that LC might be involved in antigen presentation in Chagas' disease.

scholarly journals Trypanosoma cruzi Infection Is Enhanced by Vector Saliva through Immunosuppressant Mechanisms Mediated by Lysophosphatidylcholine

2008 ◽  
Vol 76 (12) ◽  
pp. 5543-5552 ◽  
Author(s):  
Rafael D. Mesquita ◽  
Alan Brito Carneiro ◽  
André Bafica ◽  
Felipe Gazos-Lopes ◽  
Christina M. Takiya ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Biological Effects ◽  
Mouse Skin ◽  
Inflammatory Cells ◽  
Peritoneal Macrophages ◽  
Massive Number ◽  
Cruzi Infection ◽  
Cell Chemotaxis

ABSTRACT Trypanosoma cruzi, the etiological agent of Chagas disease, is transmitted by bug feces deposited on human skin during a blood meal. However, parasite infection occurs through the wound produced by insect mouthparts. Saliva of the Triatominae bug Rhodnius prolixus is a source of lysophosphatidylcholine (LPC). Here, we tested the role of both triatomine saliva and LPC on parasite transmission. We show that vector saliva is a powerful inducer of cell chemotaxis. A massive number of inflammatory cells were found at the sites where LPC or saliva was inoculated into the skin of mice. LPC is a known chemoattractant for monocytes, but neutrophil recruitment induced by saliva is LPC independent. The preincubation of peritoneal macrophages with saliva or LPC increased fivefold the association of T. cruzi with these cells. Moreover, saliva and LPC block nitric oxide production by T. cruzi-exposed macrophages. The injection of saliva or LPC into mouse skin in the presence of the parasite induces an up-to-sixfold increase in blood parasitemia. Together, our data suggest that saliva of the Triatominae enhances T. cruzi transmission and that some of its biological effects are attributed to LPC. This is a demonstration that a vector-derived lysophospholipid may act as an enhancing factor of Chagas disease.

Dynamics of T Cells Repertoire During Trypanosoma cruzi Infection and its Post-Treatment Modulation

2019 ◽  
Vol 26 (36) ◽  
pp. 6519-6543 ◽  
Author(s):  
Adriana Egui ◽  
Paola Lasso ◽  
Elena Pérez-Antón ◽  
M. Carmen Thomas ◽  
Manuel Carlos López
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Cardiac Tissue ◽  
Acute Infection ◽  
Clinical Status ◽  
Chronic Phase ◽  
Parasite Load ◽  
Chronic Patients ◽  
Cruzi Infection

Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host’s immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.

scholarly journals Absence of Bim sensitizes mice to experimental Trypanosoma cruzi infection

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Marcela Hernández-Torres ◽  
Rogério Silva do Nascimento ◽  
Monica Cardozo Rebouças ◽  
Alexandra Cassado ◽  
Kely Catarine Matteucci ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasite Load ◽  
Peritoneal Macrophages ◽  
T Cell Response ◽  
No Production ◽  
Similar Reduction ◽  
Ifn Γ

AbstractChagas disease is a life-threatening disorder caused by the protozoan parasite Trypanosoma cruzi. Parasite-specific antibodies, CD8+ T cells, as well as IFN-γ and nitric oxide (NO) are key elements of the adaptive and innate immunity against the extracellular and intracellular forms of the parasite. Bim is a potent pro-apoptotic member of the Bcl-2 family implicated in different aspects of the immune regulation, such as negative selection of self-reactive thymocytes and elimination of antigen-specific T cells at the end of an immune response. Interestingly, the role of Bim during infections remains largely unidentified. To explore the role of Bim in Chagas disease, we infected WT, Bim+/−, Bim−/− mice with trypomastigotes forms of the Y strain of T. cruzi. Strikingly, our data revealed that Bim−/− mice exhibit a delay in the development of parasitemia followed by a deficiency in the control of parasite load in the bloodstream and a decreased survival compared to WT and Bim+/− mice. At the peak of parasitemia, peritoneal macrophages of Bim−/− mice exhibit decreased NO production, which correlated with a decrease in the pro-inflammatory Small Peritoneal Macrophage (SPM) subset. A similar reduction in NO secretion, as well as in the pro-inflammatory cytokines IFN-γ and IL-6, was also observed in Bim−/− splenocytes. Moreover, an impaired anti-T. cruzi CD8+ T-cell response was found in Bim−/− mice at this time point. Taken together, our results suggest that these alterations may contribute to the establishment of a delayed yet enlarged parasitic load observed at day 9 after infection of Bim−/− mice and place Bim as an important protein in the control of T. cruzi infections.

scholarly journals Neurotrophin Receptor TrkC Is an Entry Receptor for Trypanosoma cruzi in Neural, Glial, and Epithelial Cells

2011 ◽  
Vol 79 (10) ◽  
pp. 4081-4087 ◽  
Author(s):  
Craig Weinkauf ◽  
Ryan Salvador ◽  
Mercio PereiraPerrin
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Mammalian Cells ◽  
Chinese Hamster ◽  
Neuronal Cell ◽  
Host Cells ◽  
Neurotrophin Receptor ◽  
Content Type

ABSTRACTTrypanosoma cruzi, the agent of Chagas' disease, infects a variety of mammalian cells in a process that includes multiple cycles of intracellular division and differentiation starting with host receptor recognition by a parasite ligand(s). Earlier work in our laboratory showed that the neurotrophin-3 (NT-3) receptor TrkC is activated byT. cruzisurfacetrans-sialidase, also known as parasite-derived neurotrophic factor (PDNF). However, it has remained unclear whether TrkC is used byT. cruzito enter host cells. Here, we show that a neuronal cell line (PC12-NNR5) relatively resistant toT. cruzibecame highly susceptible to infection when overexpressing human TrkC but not human TrkB. Furthermore,trkCtransfection conferred an ∼3.0-fold intracellular growth advantage. Sialylation-deficient Chinese hamster ovarian (CHO) epithelial cell lines Lec1 and Lec2 also became much more permissive toT. cruziafter transfection with thetrkCgene. Additionally, NT-3 specifically blockedT. cruziinfection of the TrkC-NNR5 transfectants and of naturally permissive TrkC-bearing Schwann cells and astrocytes, as did recombinant PDNF. Two specific inhibitors of Trk autophosphorylation (K252a and AG879) and inhibitors of Trk-induced MAPK/Erk (U0126) and Akt kinase (LY294002) signaling, but not an inhibitor of insulin-like growth factor 1 receptor, abrogated TrkC-mediated cell invasion. Antibody to TrkC blockedT. cruziinfection of the TrkC-NNR5 transfectants and of cells that naturally express TrkC. The TrkC antibody also significantly and specifically reduced cutaneous infection in a mouse model of acute Chagas' disease. TrkC is ubiquitously expressed in the peripheral and central nervous systems, and in nonneural cells infected byT. cruzi, including cardiac and gastrointestinal muscle cells. Thus, TrkC is implicated as a functional PDNF receptor in cell entry, independently of sialic acid recognition, mediating broadT. cruziinfection bothin vitroandin vivo.

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