Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages

Macrophages play an important role in human immunodeficiency virus (HIV) pathogenesis and contribute to establishment of a viral reservoir responsible for continuous virus production and virus transmission to T cells. In this study, we investigated the differences between various monocyte-derived ma...

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Main Authors: Elisabeth A. Diget, Kaja Zuwala, Randi K. Berg, Rune R. Laursen, Stine Søby, Lars Østergaard, Jesper Melchjorsen, Trine H. Mogensen
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/208412
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author Elisabeth A. Diget
Kaja Zuwala
Randi K. Berg
Rune R. Laursen
Stine Søby
Lars Østergaard
Jesper Melchjorsen
Trine H. Mogensen
author_facet Elisabeth A. Diget
Kaja Zuwala
Randi K. Berg
Rune R. Laursen
Stine Søby
Lars Østergaard
Jesper Melchjorsen
Trine H. Mogensen
author_sort Elisabeth A. Diget
collection DOAJ
description Macrophages play an important role in human immunodeficiency virus (HIV) pathogenesis and contribute to establishment of a viral reservoir responsible for continuous virus production and virus transmission to T cells. In this study, we investigated the differences between various monocyte-derived macrophages (MDMs) generated through different differentiation protocols and evaluated different cellular, immunological, and virological properties. We found that elevated and persistent HIV-1 pWT/BaL replication could be obtained only in MDMs grown in RPMI containing macrophage colony-stimulating factor (M-CSF). Interestingly, this MDM type was also most responsive to toll-like receptor stimulation. By contrast, all MDM types were activated to a comparable extent by intracellular DNA, and the macrophage serum-free medium-(Mac-SFM-)differentiated MDMs responded strongly to membrane fusion through expression of CXCL10. Finally, we found that HIV infection of RPMI/M-CSF-differentiated MDMs induced low-grade expression of two interferon-stimulated genes in some donors. In conclusion, our study demonstrates that the differentiation protocol used greatly influences the ability of MDMs to activate innate immune reactions and support HIV-1 replication. Paradoxically, the data show that the MDMs with the strongest innate immune response were also the most permissive for HIV-1 replication.
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spelling doaj-art-6d1d2d9709754c578161dd7559a7f4172025-02-03T06:12:22ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/208412208412Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived MacrophagesElisabeth A. Diget0Kaja Zuwala1Randi K. Berg2Rune R. Laursen3Stine Søby4Lars Østergaard5Jesper Melchjorsen6Trine H. Mogensen7Department of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkMacrophages play an important role in human immunodeficiency virus (HIV) pathogenesis and contribute to establishment of a viral reservoir responsible for continuous virus production and virus transmission to T cells. In this study, we investigated the differences between various monocyte-derived macrophages (MDMs) generated through different differentiation protocols and evaluated different cellular, immunological, and virological properties. We found that elevated and persistent HIV-1 pWT/BaL replication could be obtained only in MDMs grown in RPMI containing macrophage colony-stimulating factor (M-CSF). Interestingly, this MDM type was also most responsive to toll-like receptor stimulation. By contrast, all MDM types were activated to a comparable extent by intracellular DNA, and the macrophage serum-free medium-(Mac-SFM-)differentiated MDMs responded strongly to membrane fusion through expression of CXCL10. Finally, we found that HIV infection of RPMI/M-CSF-differentiated MDMs induced low-grade expression of two interferon-stimulated genes in some donors. In conclusion, our study demonstrates that the differentiation protocol used greatly influences the ability of MDMs to activate innate immune reactions and support HIV-1 replication. Paradoxically, the data show that the MDMs with the strongest innate immune response were also the most permissive for HIV-1 replication.http://dx.doi.org/10.1155/2013/208412
spellingShingle Elisabeth A. Diget
Kaja Zuwala
Randi K. Berg
Rune R. Laursen
Stine Søby
Lars Østergaard
Jesper Melchjorsen
Trine H. Mogensen
Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages
Mediators of Inflammation
title Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages
title_full Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages
title_fullStr Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages
title_full_unstemmed Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages
title_short Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages
title_sort characterization of hiv 1 infection and innate sensing in different types of primary human monocyte derived macrophages
url http://dx.doi.org/10.1155/2013/208412
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