Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human monocyte-derived macrophages infected in vitro with wild type Leishmania chagasi parasites and then cultured with naive, autologous T-cells

ABSTRACT: We performed gene expression analysis using Affymetrix U133Plus2 microarray chips on cultures of infected human cells. To mimic an in vivo infection, we infected human monocyte-derived macrophages (MDMs) in vitro with wild-type L. chagasi parasites and then co-cultured those infected MDMs with naive, autologous T-cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Nicholas Ettinger

PROVIDER: E-MEXP-1290 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Macrophage and T-cell gene expression in a model of early infection with the protozoan Leishmania chagasi.

Ettinger Nicholas A NA Wilson Mary E ME

PLoS neglected tropical diseases 20080625 6

Visceral leishmaniasis is a potentially fatal infectious disease caused by the protozoan parasite Leishmania infantum/chagasi in the New World, or by L. donovani or L. infantum/chagasi in the Old World. Infection leads to a variety of outcomes ranging from asymptomatic infection to active disease, characterized by fevers, cachexia, hepatosplenomegaly and suppressed immune responses. We reasoned that events occurring during the initial few hours when the parasite encounters cells of the innate an ...[more]

PMID: 18575603

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Project description:Leishmania (L.) are obligated intracellular protozoan parasites that develop electively in macrophages. These cells that are acting as a safe shelter for the pathogens but also as their ultimate killer, making them the alpha and the omega during leishmaniasis diseases. Macrophages are able to secrete a remarkably diverse set of regulators known to influence the physiological functions and differentiation of neighboring cells to trigger an adaptive immune response of protective Th1-type cells, whereas parasites have developed a wide range of mechanisms to circumvent the hostâs immune responses. Most of our understanding of this host-parasite conflict, in the context of macrophage invasion by L. major metacyclic promastigotes, has been gleaned from studies investigating the macrophage responses at late and unique time points after infection. To investigate the dynamics of this duel, we have analyzed the transciptomic profile of monocyte-derived human macrophages at different time points during the first 24h upon in vitro infection using high throughput microarray platform. The gene expression profile of 17,838 genes showed high expression variability between the three human donors at different time points post infection. Cross comparison between the three donors allowed the identification of a common set of expressed genes coding for inflammatory and chemotactic molecules, transcription factors, apoptosis inhibition, glucose synthesis and heme metabolism. The findings presented in this work suggest that transcriptome dynamics of macrophages early during the first 24h post infection enable to identify novel key pathways deregulated upon L. major invasion. Our reported set of expressed genes will be useful in future rounds of data mining and functional analyses. In total 27 samples from three different donors were analyzed. For each donor, samples at 0h, 3h, 6h, 12h and 24h of culture were used as controls. For each donor, samples of cells infected with metacyclic Leishmania major parasites at 3h, 6h, 12h and 24h post-infection were analyzed.

Dataset Information

Transcription profiling of human monocyte-derived macrophages infected in vitro with wild type Leishmania chagasi parasites and then cultured with naive, autologous T-cells

Publications

Macrophage and T-cell gene expression in a model of early infection with the protozoan Leishmania chagasi.

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