Abstract
Host cell infection by the intracellular pathogen, Trypanosoma cruzi, involves activation of signaling pathways, cytoskeletal reorganization, and targeted recruitment of host cell lysosomes. To determine the consequences of T. cruzi invasion on host cell gene expression, high density microarrays consisting of approximately 27,000 human cDNAs were hybridized with fluorescent probes generated from T. cruzi-infected human fibroblasts (HFF) at early time points following infection (2-24 h). Surprisingly, no genes were induced > or =2-fold in HFF between 2 and 6 h post-infection (hpi) in repeated experiments while immediate repression of six host cell transcripts was observed. A significant increase in transcript abundance for 106 host cell genes was observed at 24 hpi. Among the most highly induced is a set of interferon-stimulated genes, indicative of a type I interferon (IFN) response to T. cruzi. In support of this, T. cruzi-infected fibroblasts begin to secrete IFNbeta at 18 hpi following the induction of IFNbeta transcripts. As compared with global transcriptional responses evoked by other intracellular pathogens, T. cruzi is a stealth parasite that elicits few changes in host cell transcription during the initiation of infection.
Highlights
Global transcriptional responses elicited in mammalian cells by pathogenic organisms are predicted to provide a unique signature of the particular interaction [1]
Temporal Analysis of Host Cell Gene Expression Reveals a Marked Delay in T. cruzi-induced Transcriptional Response— The global transcriptional response elicited in human fibroblasts to infective T. cruzi trypomastigotes was determined using cDNA microarray hybridization
Arrays were hybridized with Cy5-labeled human foreskin fibroblasts (HFF) cDNA and Cy3-labeled cDNA consisting of HFF:T. cruzi (4:1) generated to mimic the estimated amount of parasite RNA present in samples prepared from infected cells
Summary
Global transcriptional responses elicited in mammalian cells by pathogenic organisms are predicted to provide a unique signature of the particular interaction [1]. Signaling pathways that are rapidly activated in both the host cell and the parasite are known to regulate T. cruzi entry into mammalian cells. To further dissect the molecular events regulating early T. cruzi-host cell interactions, we have employed cDNA microarray hybridization to define the temporal host cell transcriptional response induced by infection with T. cruzi trypomastigotes. To facilitate comparisons to existing microarray data bases, which define temporal host cell transcriptional responses to the intracellular pathogens, Toxoplasma gondii [14] and human cytomegalovirus [6], primary human foreskin fibroblasts (HFF) were used in this study. As compared with the rapid changes in host cell transcript abundance elicited by other intracellular pathogens, T. cruzi is highly unique in its ability to initiate the infectious process without inducing gene expression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
