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Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses.

Millar JA, Valdés R, Kacharia FR, Landfear SM, Cambronne ED, Raghavan R - Front Microbiol (2015)

Bottom Line: At 5 days post-infection, when compared to uninfected cells, 1057 genes were differentially expressed (746 genes up-regulated and 311 genes down-regulated) in C. burnetii infected cells, whereas 698 genes (534 genes up-regulated and 164 genes down-regulated) were differentially expressed in L. mexicana infected cells.Additionally, we detected 257 micro RNAs (miRNAs) that were expressed in THP-1 cells, and identified miRNAs that were specifically expressed during Coxiella or Leishmania infections.Collectively, this study identified host mRNAs and miRNAs that were influenced by Coxiella and/or Leishmania infections, and our data indicate that although their PVs are morphologically similar, Coxiella and Leishmania have evolved different strategies that perturb distinct host processes to create and thrive within their respective intracellular niches.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology and Center for Life in Extreme Environments, Portland State University, Portland, OR USA.

ABSTRACT
Coxiella burnetii is a bacterium that thrives in an acidic parasitophorous vacuole (PV) derived from lysosomes. Leishmania mexicana, a eukaryote, has also independently evolved to live in a morphologically similar PV. As Coxiella and Leishmania are highly divergent organisms that cause different diseases, we reasoned that their respective infections would likely elicit distinct host responses despite producing phenotypically similar parasite-containing vacuoles. The objective of this study was to investigate, at the molecular level, the macrophage response to each pathogen. Infection of THP-1 (human monocyte/macrophage) cells with Coxiella and Leishmania elicited disparate host responses. At 5 days post-infection, when compared to uninfected cells, 1057 genes were differentially expressed (746 genes up-regulated and 311 genes down-regulated) in C. burnetii infected cells, whereas 698 genes (534 genes up-regulated and 164 genes down-regulated) were differentially expressed in L. mexicana infected cells. Interestingly, of the 1755 differentially expressed genes identified in this study, only 126 genes (~7%) are common to both infections. We also discovered that 1090 genes produced mRNA isoforms at significantly different levels under the two infection conditions, suggesting that alternate proteins encoded by the same gene might have important roles in host response to each infection. Additionally, we detected 257 micro RNAs (miRNAs) that were expressed in THP-1 cells, and identified miRNAs that were specifically expressed during Coxiella or Leishmania infections. Collectively, this study identified host mRNAs and miRNAs that were influenced by Coxiella and/or Leishmania infections, and our data indicate that although their PVs are morphologically similar, Coxiella and Leishmania have evolved different strategies that perturb distinct host processes to create and thrive within their respective intracellular niches.

No MeSH data available.


Related in: MedlinePlus

Protein-protein interaction analysis. Protein-protein interaction networks of up-regulated genes in (A)C. burnetii-infected and (B)L. mexicana-infected THP1 cells visualized in STRING. Colors based on Markov Clustering with an inflation factor of 2. Highlighted clusters are labeled with their GO or KEGG categories.
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Figure 2: Protein-protein interaction analysis. Protein-protein interaction networks of up-regulated genes in (A)C. burnetii-infected and (B)L. mexicana-infected THP1 cells visualized in STRING. Colors based on Markov Clustering with an inflation factor of 2. Highlighted clusters are labeled with their GO or KEGG categories.

Mentions: A protein–protein interaction network analysis using the STRING database (Franceschini et al., 2013) confirmed that Coxiella infection induced the expression of genes involved in negative regulation of cell death (Figure 2A). In contrast, this analysis identified that genes involved in positive regulation of cell death were upregulated in Leishmania-infected cells (Figure 2B). We confirmed this trend by analyzing the expression of a subset of cell death-related genes using qPCR (Additional File Supplementary Figure S1). The induction of host cell death during later stages of infection probably aids in the cell-to-cell transfer of Leishmania amastigotes within membrane blebs, as shown recently (Real et al., 2014).


Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses.

Millar JA, Valdés R, Kacharia FR, Landfear SM, Cambronne ED, Raghavan R - Front Microbiol (2015)

Protein-protein interaction analysis. Protein-protein interaction networks of up-regulated genes in (A)C. burnetii-infected and (B)L. mexicana-infected THP1 cells visualized in STRING. Colors based on Markov Clustering with an inflation factor of 2. Highlighted clusters are labeled with their GO or KEGG categories.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528172&req=5

Figure 2: Protein-protein interaction analysis. Protein-protein interaction networks of up-regulated genes in (A)C. burnetii-infected and (B)L. mexicana-infected THP1 cells visualized in STRING. Colors based on Markov Clustering with an inflation factor of 2. Highlighted clusters are labeled with their GO or KEGG categories.
Mentions: A protein–protein interaction network analysis using the STRING database (Franceschini et al., 2013) confirmed that Coxiella infection induced the expression of genes involved in negative regulation of cell death (Figure 2A). In contrast, this analysis identified that genes involved in positive regulation of cell death were upregulated in Leishmania-infected cells (Figure 2B). We confirmed this trend by analyzing the expression of a subset of cell death-related genes using qPCR (Additional File Supplementary Figure S1). The induction of host cell death during later stages of infection probably aids in the cell-to-cell transfer of Leishmania amastigotes within membrane blebs, as shown recently (Real et al., 2014).

Bottom Line: At 5 days post-infection, when compared to uninfected cells, 1057 genes were differentially expressed (746 genes up-regulated and 311 genes down-regulated) in C. burnetii infected cells, whereas 698 genes (534 genes up-regulated and 164 genes down-regulated) were differentially expressed in L. mexicana infected cells.Additionally, we detected 257 micro RNAs (miRNAs) that were expressed in THP-1 cells, and identified miRNAs that were specifically expressed during Coxiella or Leishmania infections.Collectively, this study identified host mRNAs and miRNAs that were influenced by Coxiella and/or Leishmania infections, and our data indicate that although their PVs are morphologically similar, Coxiella and Leishmania have evolved different strategies that perturb distinct host processes to create and thrive within their respective intracellular niches.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology and Center for Life in Extreme Environments, Portland State University, Portland, OR USA.

ABSTRACT
Coxiella burnetii is a bacterium that thrives in an acidic parasitophorous vacuole (PV) derived from lysosomes. Leishmania mexicana, a eukaryote, has also independently evolved to live in a morphologically similar PV. As Coxiella and Leishmania are highly divergent organisms that cause different diseases, we reasoned that their respective infections would likely elicit distinct host responses despite producing phenotypically similar parasite-containing vacuoles. The objective of this study was to investigate, at the molecular level, the macrophage response to each pathogen. Infection of THP-1 (human monocyte/macrophage) cells with Coxiella and Leishmania elicited disparate host responses. At 5 days post-infection, when compared to uninfected cells, 1057 genes were differentially expressed (746 genes up-regulated and 311 genes down-regulated) in C. burnetii infected cells, whereas 698 genes (534 genes up-regulated and 164 genes down-regulated) were differentially expressed in L. mexicana infected cells. Interestingly, of the 1755 differentially expressed genes identified in this study, only 126 genes (~7%) are common to both infections. We also discovered that 1090 genes produced mRNA isoforms at significantly different levels under the two infection conditions, suggesting that alternate proteins encoded by the same gene might have important roles in host response to each infection. Additionally, we detected 257 micro RNAs (miRNAs) that were expressed in THP-1 cells, and identified miRNAs that were specifically expressed during Coxiella or Leishmania infections. Collectively, this study identified host mRNAs and miRNAs that were influenced by Coxiella and/or Leishmania infections, and our data indicate that although their PVs are morphologically similar, Coxiella and Leishmania have evolved different strategies that perturb distinct host processes to create and thrive within their respective intracellular niches.

No MeSH data available.


Related in: MedlinePlus