Changes in the Expression of Human Cell Division Autoantigen-1 Influence Toxoplasma gondii Growth and Development
نویسندگان
چکیده
Toxoplasma is a significant opportunistic pathogen in AIDS, and bradyzoite differentiation is the critical step in the pathogenesis of chronic infection. Bradyzoite development has an apparent tropism for cells and tissues of the central nervous system, suggesting the need for a specific molecular environment in the host cell, but it is unknown whether this environment is parasite directed or the result of molecular features specific to the host cell itself. We have determined that a trisubstituted pyrrole acts directly on human and murine host cells to slow tachyzoite replication and induce bradyzoite-specific gene expression in type II and III strain parasites but not type I strains. New mRNA synthesis in the host cell was required and indicates that novel host transcripts encode signals that were able to induce parasite development. We have applied multivariate microarray analyses to identify and correlate host gene expression with specific parasite phenotypes. Human cell division autoantigen-1 (CDA1) was identified in this analysis, and small interfering RNA knockdown of this gene demonstrated that CDA1 expression causes the inhibition of parasite replication that leads subsequently to the induction of bradyzoite differentiation. Overexpression of CDA1 alone was able to slow parasite growth and induce the expression of bradyzoite-specific proteins, and thus these results demonstrate that changes in host cell transcription can directly influence the molecular environment to enable bradyzoite development. Investigation of host biochemical pathways with respect to variation in strain type response will help provide an understanding of the link(s) between the molecular environment in the host cell and parasite development.
منابع مشابه
Manipulation of IL-10 gene expression by Toxoplasma gondii and its products
Background: This study was designed to evaluate whether or not T. gondii and its derivatives can change the gene expression level of IL-10 in murine leukocytes in vivo. Methods: Fifty BALB/c mice were divided into 5 groups, four of which received the excretory/secretory product (ESP) from cell culture medium, the ESP from cell free medium, the Toxoplasma lysate product (TLP) and the a...
متن کاملDevelopment of a Lateral Flow Immunoassay Using Recombinant Dense Granular Antigen (GRA) 7 to Detect Anti-Toxoplasma gondii IgG Antibodies
Toxoplasma gondii is an intracellular protozoan parasite that causes toxoplasmosis and is of medical importance in pregnant women and immunosuppressed patients. In recent years, many methods have been developed for the detection of infection caused by this parasite; however, most of the developed methods are not adequately sensitive. The dense granular antigen (GRA) ...
متن کاملConstruction, Expression and Preliminary Immunological Evaluation of a DNA Plasmid Encoding the GRA2 Protein of Toxoplasma gondii
Toxoplasmosis is a worldwide infection which is commonly asymptomatic but can cause serious medical problems in immunocompromised individuals and fetus. The infection also causes considerable economic loss because of abortion in livestock, mostly in sheep and goats. DNA vaccination may be a powerful approach against intracellular parasites such as Toxoplasma gondii. The goal of this study was t...
متن کاملCloning rhoptry protein 1 (ROP1) gene of Toxoplasma gondii (RH) in expression vector
Toxoplasma gondii contain various immunogenic antigens. The most important Toxoplasma antigens are somatic and excreted/secreted antigens. Rhoptry proteins are known as excreted/secreted antigens. These antigens have been proposed as a vaccine candidate against toxoplasmosis. The main objective of the present work was cloning rhoptry protein1 (ROP1) Gene of Toxoplasma gondii (RH) in a cloning...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- PLoS Pathogens
دوره 2 شماره
صفحات -
تاریخ انتشار 2006