scholarly journals Intranasal Vaccinations with the trans-Sialidase Antigen plus CpG Adjuvant Induce Mucosal Immunity Protective against Conjunctival Trypanosoma cruzi Challenges

2010 ◽  
Vol 78 (3) ◽  
pp. 1333-1338 ◽  
Author(s):  
O. K. Giddings ◽  
C. S. Eickhoff ◽  
N. L. Sullivan ◽  
D. F. Hoft
Keyword(s):  
Trypanosoma Cruzi ◽  
Immune Responses ◽  
Body Fluid ◽  
Direct Evidence ◽  
Protozoan Parasite ◽  
Secretory Iga ◽  
Parasite Invasion ◽  
Mucosal Surfaces ◽  
Parasite Replication ◽  
Intracellular Protozoan Parasite

ABSTRACT Trypanosoma cruzi is an intracellular protozoan parasite capable of infecting through mucosal surfaces. Our laboratory has previously elucidated the anatomical routes of infection after both conjunctival and gastric challenge in mice. We have shown that chronically infected mice develop strong immune responses capable of protecting against subsequent rechallenge with virulent parasites through gastric, conjunctival, and systemic routes of infection. We have also shown that intranasal immunizations with the unique T. cruzi trans-sialidase (TS) antigen protect against gastric and systemic T. cruzi challenge. In the current work we have investigated the ability of purified TS adjuvanted with CpG-containing oligonucleotides to induce immunity against conjunctival T. cruzi challenge. We confirm that intranasal vaccinations with TS plus CpG induce TS-specific T-cell and secretory IgA responses. TS-specific secretory IgA was detectable in the tears of vaccinated mice, the initial body fluid that contacts the parasite during infectious conjunctival exposures. We further show that intranasal vaccinations with TS plus CpG protect against conjunctival T. cruzi challenge, limiting local parasite replication at the site of mucosal invasion and systemic parasite dissemination. We also provide the first direct evidence that mucosal antibodies induced by intranasal TS vaccination can inhibit parasite invasion.

Temperature, Mitochondria, and Reye's Syndrome

PEDIATRICS ◽  
1983 ◽  
Vol 71 (6) ◽  
pp. 985-985
Author(s):  
RIF S. EL-MALLAKH
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Protozoan Parasite ◽  
Mitochondrial Enzyme ◽  
Reye's Syndrome ◽  
Electron Microscopic ◽  
Microscopic Studies ◽  
Mitochondrial Defect ◽  
Intracellular Protozoan Parasite

To the Editor.— Mitochondrial failure, manifest by changes in mitochondrial enzyme activity1-3 and morphology,4-5 is central to Reye's syndrome (RS).6 Although it has been variously hypothesized that the mitochondrial changes are secondary to an exogenous toxin,7-12 or an intrinsic mitochondrial defect,6 the actual cause remains obscure. Electron microscopic studies have shown sweelling and loss of cristate in mitochondria of patients with RS. It is interesting that very similar changes occur in Trypanosoma cruzi.13-16 T cruzi is an extracellular/intracellular protozoan parasite which causes Chagas' disease.17

scholarly journals Motility patterns of Trypanosoma cruzi trypomastigotes correlate with the efficiency of parasite invasion in vitro

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jorge A. Arias-del-Angel ◽  
Jesús Santana-Solano ◽  
Moisés Santillán ◽  
Rebeca G. Manning-Cela
Keyword(s):  
Trypanosoma Cruzi ◽  
Cell Line ◽  
Mammalian Cells ◽  
Dependent Manner ◽  
Parasite Invasion ◽  
Mammalian Cell Cultures ◽  
A Cell ◽  
Parasite Replication ◽  
Parasite Motility

Abstract Numerous works have demonstrated that trypanosomatid motility is relevant for parasite replication and sensitivity. Nonetheless, although some findings indirectly suggest that motility also plays an important role during infection, this has not been extensively investigated. This work is aimed at partially filling this void for the case of Trypanosoma cruzi. After recording swimming T. cruzi trypomastigotes (CL Brener strain) and recovering their individual trajectories, we statistically analyzed parasite motility patterns. We did this with parasites that swim alone or above monolayer cultures of different cell lines. Our results indicate that T. cruzi trypomastigotes change their motility patterns when they are in the presence of mammalian cells, in a cell-line dependent manner. We further performed infection experiments in which each of the mammalian cell cultures were incubated for 2 h together with trypomastigotes, and measured the corresponding invasion efficiency. Not only this parameter varied from cell line to cell line, but it resulted to be positively correlated with the corresponding intensity of the motility pattern changes. Together, these results suggest that T. cruzi trypomastigotes are capable of sensing the presence of mammalian cells and of changing their motility patterns accordingly, and that this might increase their invasion efficiency.

scholarly journals The major 85-kD surface antigen of the mammalian form of Trypanosoma cruzi is encoded by a large heterogeneous family of simultaneously expressed genes.

1990 ◽  
Vol 172 (2) ◽  
pp. 589-597 ◽  
Author(s):  
S Kahn ◽  
W C Van Voorhis ◽  
H Eisen
Keyword(s):  
Trypanosoma Cruzi ◽  
Gene Family ◽  
Protozoan Parasite ◽  
Surface Antigens ◽  
African Trypanosomes ◽  
Antigenic Diversity ◽  
Obligate Intracellular ◽  
The Family ◽  
Large Repertoire ◽  
Intracellular Protozoan Parasite

Trypanosoma cruzi is an obligate intracellular protozoan parasite. The parasite mammalian stage surface antigens exhibit extensive antigenic diversity. We have characterized a family of T. cruzi genes that code for a polymorphic set of 85-kD surface antigens, the SA85-1 antigens. The family contains greater than 100 genes and pseudogenes, of which a minimum of nine are transcribed. The gene family is expressed in the mammalian stage only. A subset of the gene family is present in two telomere-linked copies in the genome. Telomere linkage of other expressed SA85-1 genes has not been demonstrated. We have shown that at least three members of the SA85-1 gene family encode antigens at the surface of the mammalian stage of the parasite. Interestingly, these three antigens are expressed on all the trypanosomes examined. This suggests that T. cruzi simultaneously expresses a large repertoire of similar, but diverse antigens at its surface. Thus, T. cruzi exhibits extensive antigenic diversity in a system unique from that of African trypanosomes, perhaps reflecting its intracellular niche.

scholarly journals Transcriptome analysis of alternative splicing in the pathogen life cycle in human foreskin fibroblasts infected with Trypanosoma cruzi

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hyeim Jung ◽  
Seonggyun Han ◽  
Younghee Lee
Keyword(s):  
Life Cycle ◽  
Alternative Splicing ◽  
Trypanosoma Cruzi ◽  
Exon Skipping ◽  
Protozoan Parasite ◽  
Rna Seq ◽  
Parasite Life Cycle ◽  
Human Foreskin Fibroblasts ◽  
Insight Into ◽  
Intracellular Protozoan Parasite

Abstract Trypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease as a zoonotic pathogen. The parasite has been shown to remodel expression in the host transcriptome under different conditions. Although alternative splicing (AS) is involved in virtually every biological function in eukaryotes, including cellular differentiation and responses to immune reactions, host AS events that occur as a result of T. cruzi infection have yet to be explored. In this study, we bioinformatically investigated the transcriptome AS dynamics of T. cruzi (Y strain) infected human foreskin fibroblasts using RNA-Seq data captured over four timepoints (4, 24, 48, and 72 h post infection (hpi)). We identified 1768, 399, 250, and 299 differentially expressed exons (AS exons) at 4, 24, 48, and 72 hpi, respectively, showing that host AS mechanism may have a significant role in the intracellular life cycle of the parasite. We present an exon skipping event in HDAC7, which is a candidate gene that is important in the parasite’s cell cycle. To sum up, this bioinformatics analysis of transcriptome may provide new potential insight into AS regulation in human foreskin fibroblast (HFF) cells infected by T. cruzi and into its implication to the parasite life cycle. Moreover, identified AS genes may provide new potential molecular candidates for improving treatment.

scholarly journals Anatomical Route of Invasion and Protective Mucosal Immunity in Trypanosoma cruzi Conjunctival Infection

2006 ◽  
Vol 74 (10) ◽  
pp. 5549-5560 ◽  
Author(s):  
O. K. Giddings ◽  
C. S. Eickhoff ◽  
T. J. Smith ◽  
L. A. Bryant ◽  
D. F. Hoft
Keyword(s):  
Trypanosoma Cruzi ◽  
Mucosal Immunity ◽  
Immunoglobulin A ◽  
Protozoan Parasite ◽  
Nasolacrimal Duct ◽  
Parasite Invasion ◽  
Respiratory Epithelia ◽  
Mucosal Infection ◽  
Mucosal Vaccines ◽  
Mucosal Secretions

ABSTRACT Trypanosoma cruzi is a protozoan parasite that can initiate mucosal infection after conjunctival exposure. The anatomical route of T. cruzi invasion and spread after conjunctival parasite contamination remains poorly characterized. In the present work we have identified the sites of initial invasion and replication after contaminative conjunctival challenges with T. cruzi metacyclic trypomastigotes using a combination of immunohistochemical and real-time PCR confirmatory techniques in 56 mice between 3 and 14 days after challenge. Our results demonstrate that the predominant route of infection involves drainage of parasites through the nasolacrimal duct into the nasal cavity. Initial parasite invasion occurs within the ductal and respiratory epithelia. After successive waves of intracellular replication and cell-to-cell spread, parasites drain via local lymphatic channels to lymph nodes and then disseminate through the blood to distant tissues. This model of conjunctival challenge was used to identify immune responses associated with protection against mucosal infection. Preceding mucosal infection induces mucosal immunity, resulting in at least 50-fold reductions in recoverable tissue parasite DNA in immune mice compared to controls 10 days after conjunctival challenge (P < 0.05). Antigen-specific gamma interferon production by T cells was increased at least 100-fold in cells harvested from immune mice (P < 0.05). Mucosal secretions containing T. cruzi-specific secretory immunoglobulin A harvested from immune mice were shown to protect against mucosal parasite infection (P < 0.05), demonstrating that mucosal antibodies can play a role in T. cruzi immunity. This model provides an important tool for detailed studies of mucosal immunity necessary for the development of mucosal vaccines.

scholarly journals Galectins in Chagas Disease: A Missing Link Between Trypanosoma cruzi Infection, Inflammation, and Tissue Damage

2022 ◽  
Vol 12 ◽  
Author(s):  
Carolina V. Poncini ◽  
Alejandro F. Benatar ◽  
Karina A. Gomez ◽  
Gabriel A. Rabinovich
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Tissue Damage ◽  
Protozoan Parasite ◽  
Multiple Roles ◽  
Health Concern ◽  
Global Public Health ◽  
Parasite Invasion ◽  
Socioeconomic Consequences ◽  
Cruzi Infection

Trypanosoma cruzi, the protozoan parasite causative agent of Chagas disease, affects about seven million people worldwide, representing a major global public health concern with relevant socioeconomic consequences, particularly in developing countries. In this review, we discuss the multiple roles of galectins, a family of β-galactoside-binding proteins, in modulating both T. cruzi infection and immunoregulation. Specifically, we focus on galectin-driven circuits that link parasite invasion and inflammation and reprogram innate and adaptive immune responses. Understanding the dynamics of galectins and their β-galactoside-specific ligands during the pathogenesis of T. cruzi infection and elucidating their roles in immunoregulation, inflammation, and tissue damage offer new rational opportunities for treating this devastating neglected disease.

scholarly journals Loss of the Conserved Alveolate Kinase MAPK2 Decouples Toxoplasma Cell Growth from Cell Division

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Xiaoyu Hu ◽  
William J. O’Shaughnessy ◽  
Tsebaot G. Beraki ◽  
Michael L. Reese
Keyword(s):  
Toxoplasma Gondii ◽  
Protein Kinases ◽  
Daughter Cell ◽  
Protozoan Parasite ◽  
Productive Infection ◽  
Centrosome Duplication ◽  
Loss Of Function ◽  
Content Type ◽  
Mitogen Activated Protein ◽  
Parasite Replication

ABSTRACT Mitogen-activated protein kinases (MAPKs) are a conserved family of protein kinases that regulate signal transduction, proliferation, and development throughout eukaryotes. The apicomplexan parasite Toxoplasma gondii expresses three MAPKs. Two of these, extracellular signal-regulated kinase 7 (ERK7) and MAPKL1, have been implicated in the regulation of conoid biogenesis and centrosome duplication, respectively. The third kinase, MAPK2, is specific to and conserved throughout the Alveolata, although its function is unknown. We used the auxin-inducible degron system to determine phenotypes associated with MAPK2 loss of function in Toxoplasma. We observed that parasites lacking MAPK2 failed to duplicate their centrosomes and therefore did not initiate daughter cell budding, which ultimately led to parasite death. MAPK2-deficient parasites initiated but did not complete DNA replication and arrested prior to mitosis. Surprisingly, the parasites continued to grow and replicate their Golgi apparatus, mitochondria, and apicoplasts. We found that the failure in centrosome duplication is distinct from the phenotype caused by the depletion of MAPKL1. As we did not observe MAPK2 localization at the centrosome at any point in the cell cycle, our data suggest that MAPK2 regulates a process at a distal site that is required for the completion of centrosome duplication and the initiation of parasite mitosis. IMPORTANCE Toxoplasma gondii is a ubiquitous intracellular protozoan parasite that can cause severe and fatal disease in immunocompromised patients and the developing fetus. Rapid parasite replication is critical for establishing a productive infection. Here, we demonstrate that a Toxoplasma protein kinase called MAPK2 is conserved throughout the Alveolata and essential for parasite replication. We found that parasites lacking MAPK2 protein were defective in the initiation of daughter cell budding and were rendered inviable. Specifically, T. gondii MAPK2 (TgMAPK2) appears to be required for centrosome replication at the basal end of the nucleus, and its loss causes arrest early in parasite division. MAPK2 is unique to the Alveolata and not found in metazoa and likely is a critical component of an essential parasite-specific signaling network.

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