title: Immediate/early response to Trypanosoma cruzi infection involves minimal modulation of host cell transcription.
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.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vaena de Avalos
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Blader
authors.forename: Michael
authors.initials: M
authors.lastname: Fisher
authors.forename: John C
authors.initials: JC
authors.lastname: Boothroyd
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Burleigh
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic; D014349:Trypanosoma cruzi / Q000502:physiology*
chemical_list: D016899:Interferon-beta