Limits...
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

Identification of differentially expressed genes. Gene expression in (A)Coxiella burnetii-infected and (B)Leishmania mexicana-infected THP-1 cells in comparison to uninfected THP-1 cells are shown. Differentially expressed genes are highlighted in red and green. (C) Comparison of genes differentially expressed in C. burnetii-infected and L. mexicana-infected cells. Arrows indicate up-regulation or down-regulation of genes.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4528172&req=5

Figure 1: Identification of differentially expressed genes. Gene expression in (A)Coxiella burnetii-infected and (B)Leishmania mexicana-infected THP-1 cells in comparison to uninfected THP-1 cells are shown. Differentially expressed genes are highlighted in red and green. (C) Comparison of genes differentially expressed in C. burnetii-infected and L. mexicana-infected cells. Arrows indicate up-regulation or down-regulation of genes.

Mentions: Human monocyte/macrophage cell line THP-1 was used to evaluate host responses against C. burnetii and L. mexicana. Previous studies have investigated host responses during early stages (6–72 hpi) of infections by C. burnetii and by various Leishmania species (Ren et al., 2003; Mahapatra et al., 2010; De Muylder et al., 2011; Rabhi et al., 2012, 2013); however, because the transformation from the infective form (SCV and promastigote, respectively) to the replicative form (LCV and amastigote, respectively) occur at differing rates in the two pathogens, we analyzed a later point during infection (5 days pi) when both pathogens have generated large PVs that fill most of the host cell volume. When compared to uninfected THP-1 cells, 1057 genes (746 up-regulated and 311 down-regulated) were differentially expressed in C. burnetii infected THP-1 cells, whereas 698 genes (534 up-regulated and 164 down-regulated) were differentially expressed in L. mexicana infected cells (Figure 1, Supplementary Tables S1 and S2). Interestingly, the sets of genes affected by the two pathogens are very different. Of the 1755 total genes identified in this study, only 126 genes (~7%) are differentially expressed under both conditions, and no metabolic pathways were significantly enriched within this common set of genes (Figure 1, Supplementary Table S3). A previous study that compared THP-1 cell response to infections by Coxiella and Chlamydia trachomatis (an intracellular bacterium), reported an overlap of ~25% of genes between the two infections (Ren et al., 2003). The low overlap between the host responses to Coxiella and Leishmania, and the higher magnitude of host response to C. burnetii than that to L. mexicana possibly reflects the more distant evolutionary relationship between the bacteria and the eukaryotic parasite compared to the two bacterial pathogens previously studied. Apoptosis and host cell immune response pathways were the most significantly enriched KEGG pathways in Coxiella infected cells (Table 1), as observed in previous microarray-based studies (Ren et al., 2003; Mahapatra et al., 2010). Repression of host cell death by Coxiella has been reported previously (Lührmann and Roy, 2007; Voth et al., 2007), and is thought to promote intracellular growth of Coxiella within large PVs; conversely, induction of Toll-like Receptor signaling pathways and production of cytokines and chemokines participate in the host response to Coxiella infection.


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)

Identification of differentially expressed genes. Gene expression in (A)Coxiella burnetii-infected and (B)Leishmania mexicana-infected THP-1 cells in comparison to uninfected THP-1 cells are shown. Differentially expressed genes are highlighted in red and green. (C) Comparison of genes differentially expressed in C. burnetii-infected and L. mexicana-infected cells. Arrows indicate up-regulation or down-regulation of genes.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Identification of differentially expressed genes. Gene expression in (A)Coxiella burnetii-infected and (B)Leishmania mexicana-infected THP-1 cells in comparison to uninfected THP-1 cells are shown. Differentially expressed genes are highlighted in red and green. (C) Comparison of genes differentially expressed in C. burnetii-infected and L. mexicana-infected cells. Arrows indicate up-regulation or down-regulation of genes.
Mentions: Human monocyte/macrophage cell line THP-1 was used to evaluate host responses against C. burnetii and L. mexicana. Previous studies have investigated host responses during early stages (6–72 hpi) of infections by C. burnetii and by various Leishmania species (Ren et al., 2003; Mahapatra et al., 2010; De Muylder et al., 2011; Rabhi et al., 2012, 2013); however, because the transformation from the infective form (SCV and promastigote, respectively) to the replicative form (LCV and amastigote, respectively) occur at differing rates in the two pathogens, we analyzed a later point during infection (5 days pi) when both pathogens have generated large PVs that fill most of the host cell volume. When compared to uninfected THP-1 cells, 1057 genes (746 up-regulated and 311 down-regulated) were differentially expressed in C. burnetii infected THP-1 cells, whereas 698 genes (534 up-regulated and 164 down-regulated) were differentially expressed in L. mexicana infected cells (Figure 1, Supplementary Tables S1 and S2). Interestingly, the sets of genes affected by the two pathogens are very different. Of the 1755 total genes identified in this study, only 126 genes (~7%) are differentially expressed under both conditions, and no metabolic pathways were significantly enriched within this common set of genes (Figure 1, Supplementary Table S3). A previous study that compared THP-1 cell response to infections by Coxiella and Chlamydia trachomatis (an intracellular bacterium), reported an overlap of ~25% of genes between the two infections (Ren et al., 2003). The low overlap between the host responses to Coxiella and Leishmania, and the higher magnitude of host response to C. burnetii than that to L. mexicana possibly reflects the more distant evolutionary relationship between the bacteria and the eukaryotic parasite compared to the two bacterial pathogens previously studied. Apoptosis and host cell immune response pathways were the most significantly enriched KEGG pathways in Coxiella infected cells (Table 1), as observed in previous microarray-based studies (Ren et al., 2003; Mahapatra et al., 2010). Repression of host cell death by Coxiella has been reported previously (Lührmann and Roy, 2007; Voth et al., 2007), and is thought to promote intracellular growth of Coxiella within large PVs; conversely, induction of Toll-like Receptor signaling pathways and production of cytokines and chemokines participate in the host response to Coxiella infection.

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