Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers.

The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventi...
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Autor*in:	Enrique Martin-Gayo [verfasserIn] Maria Jose Buzon [verfasserIn] Zhengyu Ouyang [verfasserIn] Taylor Hickman [verfasserIn] Jacqueline Cronin [verfasserIn] Dina Pimenova [verfasserIn] Bruce D Walker [verfasserIn] Mathias Lichterfeld [verfasserIn] Xu G Yu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Übergeordnetes Werk:	In: PLoS Pathogens - Public Library of Science (PLoS), 2005, 11(2015), 6, p e1004930
Übergeordnetes Werk:	volume:11 ; year:2015 ; number:6, p e1004930

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1371/journal.ppat.1004930

Katalog-ID:	DOAJ023180811

Internformat


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520			\|a The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes.
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Indexfelder

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publishDate	2015
allfields	10.1371/journal.ppat.1004930 doi (DE-627)DOAJ023180811 (DE-599)DOAJ23c0d3b3e3974c70badc04b87022cec2 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Enrique Martin-Gayo verfasserin aut Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers. 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes. Immunologic diseases. Allergy Biology (General) Maria Jose Buzon verfasserin aut Zhengyu Ouyang verfasserin aut Taylor Hickman verfasserin aut Jacqueline Cronin verfasserin aut Dina Pimenova verfasserin aut Bruce D Walker verfasserin aut Mathias Lichterfeld verfasserin aut Xu G Yu verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 11(2015), 6, p e1004930 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:11 year:2015 number:6, p e1004930 https://doi.org/10.1371/journal.ppat.1004930 kostenfrei https://doaj.org/article/23c0d3b3e3974c70badc04b87022cec2 kostenfrei http://europepmc.org/articles/PMC4466270?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2015 6, p e1004930
spelling	10.1371/journal.ppat.1004930 doi (DE-627)DOAJ023180811 (DE-599)DOAJ23c0d3b3e3974c70badc04b87022cec2 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Enrique Martin-Gayo verfasserin aut Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers. 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes. Immunologic diseases. Allergy Biology (General) Maria Jose Buzon verfasserin aut Zhengyu Ouyang verfasserin aut Taylor Hickman verfasserin aut Jacqueline Cronin verfasserin aut Dina Pimenova verfasserin aut Bruce D Walker verfasserin aut Mathias Lichterfeld verfasserin aut Xu G Yu verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 11(2015), 6, p e1004930 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:11 year:2015 number:6, p e1004930 https://doi.org/10.1371/journal.ppat.1004930 kostenfrei https://doaj.org/article/23c0d3b3e3974c70badc04b87022cec2 kostenfrei http://europepmc.org/articles/PMC4466270?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2015 6, p e1004930
allfields_unstemmed	10.1371/journal.ppat.1004930 doi (DE-627)DOAJ023180811 (DE-599)DOAJ23c0d3b3e3974c70badc04b87022cec2 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Enrique Martin-Gayo verfasserin aut Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers. 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes. Immunologic diseases. Allergy Biology (General) Maria Jose Buzon verfasserin aut Zhengyu Ouyang verfasserin aut Taylor Hickman verfasserin aut Jacqueline Cronin verfasserin aut Dina Pimenova verfasserin aut Bruce D Walker verfasserin aut Mathias Lichterfeld verfasserin aut Xu G Yu verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 11(2015), 6, p e1004930 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:11 year:2015 number:6, p e1004930 https://doi.org/10.1371/journal.ppat.1004930 kostenfrei https://doaj.org/article/23c0d3b3e3974c70badc04b87022cec2 kostenfrei http://europepmc.org/articles/PMC4466270?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2015 6, p e1004930
allfieldsGer	10.1371/journal.ppat.1004930 doi (DE-627)DOAJ023180811 (DE-599)DOAJ23c0d3b3e3974c70badc04b87022cec2 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Enrique Martin-Gayo verfasserin aut Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers. 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes. Immunologic diseases. Allergy Biology (General) Maria Jose Buzon verfasserin aut Zhengyu Ouyang verfasserin aut Taylor Hickman verfasserin aut Jacqueline Cronin verfasserin aut Dina Pimenova verfasserin aut Bruce D Walker verfasserin aut Mathias Lichterfeld verfasserin aut Xu G Yu verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 11(2015), 6, p e1004930 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:11 year:2015 number:6, p e1004930 https://doi.org/10.1371/journal.ppat.1004930 kostenfrei https://doaj.org/article/23c0d3b3e3974c70badc04b87022cec2 kostenfrei http://europepmc.org/articles/PMC4466270?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2015 6, p e1004930
allfieldsSound	10.1371/journal.ppat.1004930 doi (DE-627)DOAJ023180811 (DE-599)DOAJ23c0d3b3e3974c70badc04b87022cec2 DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Enrique Martin-Gayo verfasserin aut Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers. 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes. Immunologic diseases. Allergy Biology (General) Maria Jose Buzon verfasserin aut Zhengyu Ouyang verfasserin aut Taylor Hickman verfasserin aut Jacqueline Cronin verfasserin aut Dina Pimenova verfasserin aut Bruce D Walker verfasserin aut Mathias Lichterfeld verfasserin aut Xu G Yu verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 11(2015), 6, p e1004930 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:11 year:2015 number:6, p e1004930 https://doi.org/10.1371/journal.ppat.1004930 kostenfrei https://doaj.org/article/23c0d3b3e3974c70badc04b87022cec2 kostenfrei http://europepmc.org/articles/PMC4466270?pdf=render kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2015 6, p e1004930
language	English
source	In PLoS Pathogens 11(2015), 6, p e1004930 volume:11 year:2015 number:6, p e1004930
sourceStr	In PLoS Pathogens 11(2015), 6, p e1004930 volume:11 year:2015 number:6, p e1004930
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Immunologic diseases. Allergy Biology (General)
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container_title	PLoS Pathogens
authorswithroles_txt_mv	Enrique Martin-Gayo @@aut@@ Maria Jose Buzon @@aut@@ Zhengyu Ouyang @@aut@@ Taylor Hickman @@aut@@ Jacqueline Cronin @@aut@@ Dina Pimenova @@aut@@ Bruce D Walker @@aut@@ Mathias Lichterfeld @@aut@@ Xu G Yu @@aut@@
publishDateDaySort_date	2015-01-01T00:00:00Z
hierarchy_top_id	501074422
id	DOAJ023180811
language_de	englisch
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callnumber-first	R - Medicine
author	Enrique Martin-Gayo
spellingShingle	Enrique Martin-Gayo misc RC581-607 misc QH301-705.5 misc Immunologic diseases. Allergy misc Biology (General) Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers.
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topic_title	RC581-607 QH301-705.5 Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers
topic	misc RC581-607 misc QH301-705.5 misc Immunologic diseases. Allergy misc Biology (General)
topic_unstemmed	misc RC581-607 misc QH301-705.5 misc Immunologic diseases. Allergy misc Biology (General)
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title	Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers.
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title_full	Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers
author_sort	Enrique Martin-Gayo
journal	PLoS Pathogens
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author_browse	Enrique Martin-Gayo Maria Jose Buzon Zhengyu Ouyang Taylor Hickman Jacqueline Cronin Dina Pimenova Bruce D Walker Mathias Lichterfeld Xu G Yu
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author-letter	Enrique Martin-Gayo
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title_sort	potent cell-intrinsic immune responses in dendritic cells facilitate hiv-1-specific t cell immunity in hiv-1 elite controllers
callnumber	RC581-607
title_auth	Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers.
abstract	The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes.
abstractGer	The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes.
abstract_unstemmed	The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes.
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container_issue	6, p e1004930
title_short	Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers.
url	https://doi.org/10.1371/journal.ppat.1004930 https://doaj.org/article/23c0d3b3e3974c70badc04b87022cec2 http://europepmc.org/articles/PMC4466270?pdf=render https://doaj.org/toc/1553-7366 https://doaj.org/toc/1553-7374
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author2	Maria Jose Buzon Zhengyu Ouyang Taylor Hickman Jacqueline Cronin Dina Pimenova Bruce D Walker Mathias Lichterfeld Xu G Yu
author2Str	Maria Jose Buzon Zhengyu Ouyang Taylor Hickman Jacqueline Cronin Dina Pimenova Bruce D Walker Mathias Lichterfeld Xu G Yu
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up_date	2024-07-03T16:11:46.129Z
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Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers.

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