Dual Transcriptome Profiling of <italic toggle="yes">Leishmania</italic>-Infected Human Macrophages Reveals Distinct Reprogramming Signatures

ABSTRACT Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling...

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Autores principales:	Maria Cecilia Fernandes, Laura A. L. Dillon, Ashton Trey Belew, Hector Corrada Bravo, David M. Mosser, Najib M. El-Sayed
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7bd8ebae9dea4956ad7c5c2eb1176dcf
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spelling	oai:doaj.org-article:7bd8ebae9dea4956ad7c5c2eb1176dcf2021-11-15T15:50:15ZDual Transcriptome Profiling of <italic toggle="yes">Leishmania</italic>-Infected Human Macrophages Reveals Distinct Reprogramming Signatures10.1128/mBio.00027-162150-7511https://doaj.org/article/7bd8ebae9dea4956ad7c5c2eb1176dcf2016-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00027-16https://doaj.org/toc/2150-7511ABSTRACT Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. IMPORTANCE Little is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures of Leishmania spp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in infection that was reduced at later time points. A similar expression pattern was observed in the parasites. Our analyses provide specific insights into the interplay between human macrophages and Leishmania parasites and constitute an important general resource for the study of how pathogens evade host defenses and modulate the functions of the cell to survive intracellularly.Maria Cecilia FernandesLaura A. L. DillonAshton Trey BelewHector Corrada BravoDavid M. MosserNajib M. El-SayedAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 3 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Maria Cecilia Fernandes Laura A. L. Dillon Ashton Trey Belew Hector Corrada Bravo David M. Mosser Najib M. El-Sayed Dual Transcriptome Profiling of <italic toggle="yes">Leishmania</italic>-Infected Human Macrophages Reveals Distinct Reprogramming Signatures
description	ABSTRACT Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. IMPORTANCE Little is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures of Leishmania spp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in infection that was reduced at later time points. A similar expression pattern was observed in the parasites. Our analyses provide specific insights into the interplay between human macrophages and Leishmania parasites and constitute an important general resource for the study of how pathogens evade host defenses and modulate the functions of the cell to survive intracellularly.
format	article
author	Maria Cecilia Fernandes Laura A. L. Dillon Ashton Trey Belew Hector Corrada Bravo David M. Mosser Najib M. El-Sayed
author_facet	Maria Cecilia Fernandes Laura A. L. Dillon Ashton Trey Belew Hector Corrada Bravo David M. Mosser Najib M. El-Sayed
author_sort	Maria Cecilia Fernandes
title	Dual Transcriptome Profiling of <italic toggle="yes">Leishmania</italic>-Infected Human Macrophages Reveals Distinct Reprogramming Signatures
title_short	Dual Transcriptome Profiling of <italic toggle="yes">Leishmania</italic>-Infected Human Macrophages Reveals Distinct Reprogramming Signatures
title_full	Dual Transcriptome Profiling of <italic toggle="yes">Leishmania</italic>-Infected Human Macrophages Reveals Distinct Reprogramming Signatures
title_fullStr	Dual Transcriptome Profiling of <italic toggle="yes">Leishmania</italic>-Infected Human Macrophages Reveals Distinct Reprogramming Signatures
title_full_unstemmed	Dual Transcriptome Profiling of <italic toggle="yes">Leishmania</italic>-Infected Human Macrophages Reveals Distinct Reprogramming Signatures
title_sort	dual transcriptome profiling of <italic toggle="yes">leishmania</italic>-infected human macrophages reveals distinct reprogramming signatures
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/7bd8ebae9dea4956ad7c5c2eb1176dcf
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Dual Transcriptome Profiling of <italic toggle="yes">Leishmania</italic>-Infected Human Macrophages Reveals Distinct Reprogramming Signatures

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