Longitudinal Analysis of Distribution and Function of Plasmacytoid Dendritic Cells in Peripheral Blood and Gut Mucosa of HIV Infected Patients
Aberrant activation of plasmacytoid dendritic cells (pDCs) with excessive production of interferon alpha (IFNα) represents one of the hallmarks of immune activation during chronic phase of human immunodeficiency virus (HIV) infection. A number of studies have shown that disruption of mucosal integri...
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| Veröffentlicht in: | The Journal of infectious diseases 2014-03, Vol.209 (6), p.940-949 |
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| creator | Lehmann, Clara Jung, Norma Förster, Katja Koch, Nora Leifeld, Ludger Fischer, Julia Mauss, Stefan Drebber, Uta Steffen, Hans Michael Romerio, Fabio Fätkenheuer, Gerd Hartmann, Pia |
| description | Aberrant activation of plasmacytoid dendritic cells (pDCs) with excessive production of interferon alpha (IFNα) represents one of the hallmarks of immune activation during chronic phase of human immunodeficiency virus (HIV) infection. A number of studies have shown that disruption of mucosal integrity in the gut is a cause of persistent immune activation. However, little is known about the role that pDCs play in this process, and our current understanding comes from the simian immunodeficiency virus macaque model. Thus, in the present study we sought to investigate the frequency and function of pDCs in peripheral blood and gut samples from HIV-infected individuals before and 6 months after initiation of antiretroviral therapy (ART). We show that circulating pDCs were depleted in ART-naive HIV+ patients, and upregulated the gut-homing receptor CD103 compared with uninfected controls. By converse, pDCs accumulated in the terminal ileum of ART-naive HIV individuals compared with controls. Baseline levels of IFNα production and markers of immune activation in gut samples of ART-naive HIV subjects were elevated. All these parameters declined after 6 months of ART. Our results suggest that in chronic HIV infection, pDCs migrate from peripheral blood to the gut-associated lymphatic tissue, where they may contribute to immune activation. |
| doi_str_mv | 10.1093/infdis/jit612 |
| format | Article |
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A number of studies have shown that disruption of mucosal integrity in the gut is a cause of persistent immune activation. However, little is known about the role that pDCs play in this process, and our current understanding comes from the simian immunodeficiency virus macaque model. Thus, in the present study we sought to investigate the frequency and function of pDCs in peripheral blood and gut samples from HIV-infected individuals before and 6 months after initiation of antiretroviral therapy (ART). We show that circulating pDCs were depleted in ART-naive HIV+ patients, and upregulated the gut-homing receptor CD103 compared with uninfected controls. By converse, pDCs accumulated in the terminal ileum of ART-naive HIV individuals compared with controls. Baseline levels of IFNα production and markers of immune activation in gut samples of ART-naive HIV subjects were elevated. All these parameters declined after 6 months of ART. Our results suggest that in chronic HIV infection, pDCs migrate from peripheral blood to the gut-associated lymphatic tissue, where they may contribute to immune activation.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jit612</identifier><identifier>PMID: 24259523</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult ; Aged ; Anti-Retroviral Agents - therapeutic use ; Biological and medical sciences ; Biopsies ; Blood ; Blood plasma ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - pathology ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - pathology ; Cytometry ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - pathology ; Female ; Fundamental and applied biological sciences. Psychology ; HIV ; HIV 1 ; HIV infections ; HIV Infections - blood ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV Infections - pathology ; HIV/AIDS ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Ileum - immunology ; Ileum - pathology ; Infectious diseases ; Interferon-alpha - biosynthesis ; Interferon-alpha - immunology ; Intestinal Mucosa - immunology ; Intestinal Mucosa - pathology ; Macaca ; Male ; Medical sciences ; Microbiology ; Middle Aged ; Mucosa ; Prospective Studies ; Simian immunodeficiency virus ; T lymphocytes ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. 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A number of studies have shown that disruption of mucosal integrity in the gut is a cause of persistent immune activation. However, little is known about the role that pDCs play in this process, and our current understanding comes from the simian immunodeficiency virus macaque model. Thus, in the present study we sought to investigate the frequency and function of pDCs in peripheral blood and gut samples from HIV-infected individuals before and 6 months after initiation of antiretroviral therapy (ART). We show that circulating pDCs were depleted in ART-naive HIV+ patients, and upregulated the gut-homing receptor CD103 compared with uninfected controls. By converse, pDCs accumulated in the terminal ileum of ART-naive HIV individuals compared with controls. Baseline levels of IFNα production and markers of immune activation in gut samples of ART-naive HIV subjects were elevated. All these parameters declined after 6 months of ART. Our results suggest that in chronic HIV infection, pDCs migrate from peripheral blood to the gut-associated lymphatic tissue, where they may contribute to immune activation.</description><subject>Adult</subject><subject>Aged</subject><subject>Anti-Retroviral Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biopsies</subject><subject>Blood</subject><subject>Blood plasma</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - pathology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - pathology</subject><subject>Cytometry</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - pathology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HIV</subject><subject>HIV 1</subject><subject>HIV infections</subject><subject>HIV Infections - blood</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - pathology</subject><subject>HIV/AIDS</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Ileum - immunology</subject><subject>Ileum - pathology</subject><subject>Infectious diseases</subject><subject>Interferon-alpha - biosynthesis</subject><subject>Interferon-alpha - immunology</subject><subject>Intestinal Mucosa - immunology</subject><subject>Intestinal Mucosa - pathology</subject><subject>Macaca</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Middle Aged</subject><subject>Mucosa</subject><subject>Prospective Studies</subject><subject>Simian immunodeficiency virus</subject><subject>T lymphocytes</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. 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Psychology</topic><topic>HIV</topic><topic>HIV 1</topic><topic>HIV infections</topic><topic>HIV Infections - blood</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - pathology</topic><topic>HIV/AIDS</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Ileum - immunology</topic><topic>Ileum - pathology</topic><topic>Infectious diseases</topic><topic>Interferon-alpha - biosynthesis</topic><topic>Interferon-alpha - immunology</topic><topic>Intestinal Mucosa - immunology</topic><topic>Intestinal Mucosa - pathology</topic><topic>Macaca</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Middle Aged</topic><topic>Mucosa</topic><topic>Prospective Studies</topic><topic>Simian immunodeficiency virus</topic><topic>T lymphocytes</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lehmann, Clara</creatorcontrib><creatorcontrib>Jung, Norma</creatorcontrib><creatorcontrib>Förster, Katja</creatorcontrib><creatorcontrib>Koch, Nora</creatorcontrib><creatorcontrib>Leifeld, Ludger</creatorcontrib><creatorcontrib>Fischer, Julia</creatorcontrib><creatorcontrib>Mauss, Stefan</creatorcontrib><creatorcontrib>Drebber, Uta</creatorcontrib><creatorcontrib>Steffen, Hans Michael</creatorcontrib><creatorcontrib>Romerio, Fabio</creatorcontrib><creatorcontrib>Fätkenheuer, Gerd</creatorcontrib><creatorcontrib>Hartmann, Pia</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lehmann, Clara</au><au>Jung, Norma</au><au>Förster, Katja</au><au>Koch, Nora</au><au>Leifeld, Ludger</au><au>Fischer, Julia</au><au>Mauss, Stefan</au><au>Drebber, Uta</au><au>Steffen, Hans Michael</au><au>Romerio, Fabio</au><au>Fätkenheuer, Gerd</au><au>Hartmann, Pia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Longitudinal Analysis of Distribution and Function of Plasmacytoid Dendritic Cells in Peripheral Blood and Gut Mucosa of HIV Infected Patients</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2014-03-15</date><risdate>2014</risdate><volume>209</volume><issue>6</issue><spage>940</spage><epage>949</epage><pages>940-949</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>Aberrant activation of plasmacytoid dendritic cells (pDCs) with excessive production of interferon alpha (IFNα) represents one of the hallmarks of immune activation during chronic phase of human immunodeficiency virus (HIV) infection. A number of studies have shown that disruption of mucosal integrity in the gut is a cause of persistent immune activation. However, little is known about the role that pDCs play in this process, and our current understanding comes from the simian immunodeficiency virus macaque model. Thus, in the present study we sought to investigate the frequency and function of pDCs in peripheral blood and gut samples from HIV-infected individuals before and 6 months after initiation of antiretroviral therapy (ART). We show that circulating pDCs were depleted in ART-naive HIV+ patients, and upregulated the gut-homing receptor CD103 compared with uninfected controls. By converse, pDCs accumulated in the terminal ileum of ART-naive HIV individuals compared with controls. Baseline levels of IFNα production and markers of immune activation in gut samples of ART-naive HIV subjects were elevated. All these parameters declined after 6 months of ART. Our results suggest that in chronic HIV infection, pDCs migrate from peripheral blood to the gut-associated lymphatic tissue, where they may contribute to immune activation.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>24259523</pmid><doi>10.1093/infdis/jit612</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of infectious diseases, 2014-03, Vol.209 (6), p.940-949 |
| issn | 0022-1899 1537-6613 |
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| source | Jstor Complete Legacy; Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection |
| subjects | Adult Aged Anti-Retroviral Agents - therapeutic use Biological and medical sciences Biopsies Blood Blood plasma CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - pathology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - pathology Cytometry Dendritic cells Dendritic Cells - immunology Dendritic Cells - pathology Female Fundamental and applied biological sciences. Psychology HIV HIV 1 HIV infections HIV Infections - blood HIV Infections - drug therapy HIV Infections - immunology HIV Infections - pathology HIV/AIDS Human immunodeficiency virus Human viral diseases Humans Ileum - immunology Ileum - pathology Infectious diseases Interferon-alpha - biosynthesis Interferon-alpha - immunology Intestinal Mucosa - immunology Intestinal Mucosa - pathology Macaca Male Medical sciences Microbiology Middle Aged Mucosa Prospective Studies Simian immunodeficiency virus T lymphocytes Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids |
| title | Longitudinal Analysis of Distribution and Function of Plasmacytoid Dendritic Cells in Peripheral Blood and Gut Mucosa of HIV Infected Patients |
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