Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset
| Autor: | Beatrice Jacquelin, Faroudy Boufassa, Simon P. Jochems, Bruno Vaslin, Nathalie Dereudre-Bosquet, Cécile Goujard, Matthew L. Albert, Thalia Garcia-Tellez, Asier Sáez-Cirión, Yoann Madec, Laurence Meyer, Caroline Passaes, Thijs Booiman, Armanda Casrouge, Nicolas Noel, Mickaël J.-Y. Ploquin, Olivier Lambotte, Camille Lécuroux, Pierre Roques, Françoise Barré-Sinoussi, Christine Rouzioux, Brigitte Boeser-Nunnink, Neeltje A. Kootstra, Gaël Petitjean, Michaela Müller-Trutwin, Asma Essat, Mathieu Angin, Mathilde Ghislain, Kathleen Gärtner, Nicolas Huot |
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| Přispěvatelé: | HIV, Inflammation et persistance, Institut Pasteur [Paris], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Régulation des Infections Rétrovirales, Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), We thank the patients and healthy donors, as well as the physicians. We thank all members of the steering committees of the French ANRS C06, C09 and C021 cohorts and those of the ACS. We thank the Centre d'Immunologie Humaine (CIH) at Institut Pasteur and the National Center for Infectious Disease Models and Innovative Therapies (IDMIT). We are grateful to veterinarians and the staff of the IDMIT animal facilities and TIPIV, Vougny, Marie-Christine, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Other departments, AII - Amsterdam institute for Infection and Immunity, Experimental Immunology, Epidémiologie des Maladies Emergentes, Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Institut Pasteur [Paris]-Pasteur-Cnam risques infectieux et émergents ( PACRI ), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratory of Viral Immune Pathogenesis, Academisch Medisch Centrum, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP] |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
HIV Infections
Monkeys Pathology and Laboratory Medicine Polymerase Chain Reaction MESH: Dogs Immunodeficiency Viruses Animal Cells [ SDV.IMM ] Life Sciences [q-bio]/Immunology MESH: Animals Biology (General) MESH: Haplorhini Mammals Flow Cytometry Immunohistochemistry 3. Good health Blood Medical Microbiology Viral Pathogens [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Disease Progression Small Intestine Cellular Types Macaque MESH : Cobalt Isotopes Primates [SDV.IMM] Life Sciences [q-bio]/Immunology QH301-705.5 Immune Cells Immunology Viremia MESH : Radiation Protection [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology Microbiology 03 medical and health sciences Genetics Humans Molecular Biology Microbial Pathogens Blood Cells MESH: Radiometry Organisms medicine.disease Virology Chemokine CXCL10 030104 developmental biology MESH: Radiation Injuries Experimental MESH : Blood Cells HIV-1 Parasitology Immunologic diseases. Allergy MESH : Radiometry Digestive System 0301 basic medicine RNA viruses CD4-Positive T-Lymphocytes Physiology Simian Acquired Immunodeficiency Syndrome Gene Expression Cell Separation CXCR3 White Blood Cells MESH : Dogs MESH: Emergencies Blood plasma MESH : Emergencies Intestine Small Medicine and Health Sciences MESH: Radiotherapy Dosage [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology MESH: Kinetics CD68 MESH : Radiotherapy Dosage T Cells Hematology Viral Load Body Fluids Haematopoiesis medicine.anatomical_structure Vertebrates Viruses [SDV.IMM]Life Sciences [q-bio]/Immunology Simian Immunodeficiency Virus MESH : Kinetics Anatomy Pathogens Research Article MESH: Cobalt Isotopes Biology Blood Plasma MESH : Maximum Allowable Concentration Immune system Old World monkeys Retroviruses medicine CXCL10 Animals MESH : Radiation Injuries Experimental Biology and life sciences MESH: Blood Cells Lentivirus MESH: Radiation Protection HIV MESH : Haplorhini Cell Biology RC581-607 Small intestine Gastrointestinal Tract Amniotes Macaca MESH : Animals MESH: Maximum Allowable Concentration |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Public Library of Science, 2016, 12 (8), pp.11-7. ⟨10.1371/journal.ppat.1005774⟩ PLoS Pathogens, 2016, 12 (8), pp.11-7. ⟨10.1371/journal.ppat.1005774⟩ PLoS pathogens, 12(8). Public Library of Science PLoS Pathogens, Public Library of Science, 2016, 12 (8), pp.11-7. 〈10.1371/journal.ppat.1005774〉 PLoS Pathogens, Vol 12, Iss 8, p e1005774 (2016) |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI) were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort), as well as during controlled and uncontrolled viremia (ANRS cohorts). We also addressed IP-10 expression levels with regards to lymphoid tissues (LT) and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker) gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10. Author Summary Chronic immune activation is a hallmark of HIV infection and contributes in multiple ways to HIV persistence. Here, we gained insights on the association between a pro-inflammatory chemokine, CXCL10/IP-10 and HIV infection in four cohorts of HIV+ individuals, studied at distinct stages of infection (before, primary and chronic stage with spontaneous- and treatment-controlled infection). We further analyzed pathogenic and non-pathogenic SIV infections to address IP-10 levels and the presence of infected cells in tissues (lymph nodes, small and large intestine). We found that elevated systemic IP-10 levels before HIV-1 infection associate with a more rapid disease progression. During primary infection, IP-10 in blood strongly correlated with the amount of infected cells in blood. The animal model showed that IP-10 expression was regionalized in the intestine and highest in the small intestine. Studies of aviremic animals suggest that high IP-10 is indicative of viral replication in lymphoid tissues. Haematopoietic cells rather than epithelial/endothelial cells mainly contributed to the IP-10 production in small intestine (jejunum). The receptor of IP-10 was highly expressed on memory CD4+ T cells, i.e. major target cells for the virus. This study contributes to our understanding of the establishment of HIV reservoirs and why IP-10 associates with HIV/AIDS. |
| Databáze: | OpenAIRE |
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