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

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 dis...

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Autores principales: Millar, Jess A., Valdés, Raquel, Kacharia, Fenil R., Landfear, Scott M., Cambronne, Eric D., Raghavan, Rahul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528172/
https://www.ncbi.nlm.nih.gov/pubmed/26300862
http://dx.doi.org/10.3389/fmicb.2015.00794
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author Millar, Jess A.
Valdés, Raquel
Kacharia, Fenil R.
Landfear, Scott M.
Cambronne, Eric D.
Raghavan, Rahul
author_facet Millar, Jess A.
Valdés, Raquel
Kacharia, Fenil R.
Landfear, Scott M.
Cambronne, Eric D.
Raghavan, Rahul
author_sort Millar, Jess A.
collection PubMed
description 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.
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spelling pubmed-45281722015-08-21 Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses Millar, Jess A. Valdés, Raquel Kacharia, Fenil R. Landfear, Scott M. Cambronne, Eric D. Raghavan, Rahul Front Microbiol Microbiology 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. Frontiers Media S.A. 2015-08-07 /pmc/articles/PMC4528172/ /pubmed/26300862 http://dx.doi.org/10.3389/fmicb.2015.00794 Text en Copyright © 2015 Millar, Valdés, Kacharia, Landfear, Cambronne and Raghavan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Millar, Jess A.
Valdés, Raquel
Kacharia, Fenil R.
Landfear, Scott M.
Cambronne, Eric D.
Raghavan, Rahul
Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses
title Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses
title_full Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses
title_fullStr Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses
title_full_unstemmed Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses
title_short Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses
title_sort coxiella burnetii and leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528172/
https://www.ncbi.nlm.nih.gov/pubmed/26300862
http://dx.doi.org/10.3389/fmicb.2015.00794
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