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Silencing of the laminin gamma-1 gene blocks Trypanosoma cruzi infection.

ABSTRACT: It is thought that Trypanosoma cruzi, the protozoan that causes Chagas' disease, modulates the extracellular matrix network to facilitate infection of human cells. However, direct evidence to document this phenomenon is lacking. Here we show that the T. cruzi gp83 ligand, a cell surface trans-sialidase-like molecule that the parasite uses to attach to host cells, increases the level of laminin gamma-1 transcript and its expression in mammalian cells, leading to an increase in cellular infection. Stable RNA interference (RNAi) with host cell laminin gamma-1 knocks down the levels of laminin gamma-1 transcript and protein expression in mammalian cells, causing a dramatic reduction in cellular infection by T. cruzi. Thus, host laminin gamma-1, which is regulated by the parasite, plays a crucial role in the early process of infection. This is the first report showing that knocking down the expression of a human gene by RNAi inhibits the infection of an intracellular parasite.

SUBMITTER: Nde PN

PROVIDER: S-EPMC1418675 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature

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Silencing of the laminin gamma-1 gene blocks Trypanosoma cruzi infection.

Nde Pius N PN Simmons Kaneatra J KJ Kleshchenko Yuliya Y YY Pratap Siddharth S Lima Maria F MF Villalta Fernando F

Infection and immunity 20060301 3

It is thought that Trypanosoma cruzi, the protozoan that causes Chagas' disease, modulates the extracellular matrix network to facilitate infection of human cells. However, direct evidence to document this phenomenon is lacking. Here we show that the T. cruzi gp83 ligand, a cell surface trans-sialidase-like molecule that the parasite uses to attach to host cells, increases the level of laminin gamma-1 transcript and its expression in mammalian cells, leading to an increase in cellular infection. ...[more]

PMID: 16495535

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Project description:Trypanosoma cruzi is an organism highly resistant to ionizing radiation. Following a dose of 500 Gy of gamma radiation, the fragmented genomic DNA is gradually reconstructed and the pattern of chromosomal bands is restored in less than 48 hours. Cell growth arrests after irradiation but, while DNA is completely fragmented, RNA maintains its integrity. In this work we compared the transcriptional profiles of irradiated and non-irradiated epimastigotes at different time points after irradiation using microarray. In total, 273 genes were differentially expressed; from these, 160 were up-regulated and 113 down-regulated. We found that genes with predicted functions are the most prevalent in the down-regulated gene category. Translation and protein metabolic processes, as well as generation of precursor of metabolites and energy pathways were affected. In contrast, the up-regulated category was mainly composed of obsolete sequences (which included some genes of the kinetoplast DNA), genes coding for hypothetical proteins, and Retrotransposon Hot Spot genes. Finally, the tyrosyl-DNA phosphodiesterase 1, a gene involved in double-strand DNA break repair process, was up-regulated. Our study demonstrated the peculiar response to ionizing radiation, raising questions about how this organism changes its gene expression to manage such a harmful stress. To evaluate the gamma radiation effect on T. cruzi epimastigote cells, two identical and independent experiments (biological replicates) were performed in triplicate. Each triplicate was composed of seven samples: cell culture growth control (not used in the microarray experiments), non-irradiated cells (used as reference sample in the microarray analysis), and five irradiated samples that had their RNA extracted immediately after irradiation (or i.a.i.), at 4, 24, 48, and 96 hours post-irradiation. Triplicates were pooled after the RNA extraction and before the purification/amplification steps. Each pool corresponding to one of the five time points was hybridized twice against the reference pool from each experiment, applying a reference time-course dye-swap design. Thus, four microarray slides for each time point were produced, two for each biological replicate, totaling 20 slides.

Dataset Information

Silencing of the laminin gamma-1 gene blocks Trypanosoma cruzi infection.

Publications

Silencing of the laminin gamma-1 gene blocks Trypanosoma cruzi infection.

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