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Impaired dendritic cell maturation in response to pandemic H1N109 influenza virus
Authors:Ruth Chin  Linda Earnest-Silviera  Claire L Gordon  Karen Olsen  Ian Barr  Lorena E Brown  David C Jackson  Joseph Torresi
Institution:1. Department of Medicine, Austin Hospital, The University of Melbourne, Heidelberg, VIC, Australia;2. Department of Infectious Diseases, Austin Hospital, Heidelberg, VIC, Australia;3. World Health Organization Laboratory for Influenza Reference and Research, North Melbourne, VIC, Australia;4. Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, Australia;1. Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands;2. Department of Otorhinolaryngology, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands;3. Department of Otorhinolaryngology, Leiden University Medical Center, Leiden, The Netherlands;4. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands;1. Department of Clinical Medicine, University of Bologna, Bologna, Italy;2. Operative Unit of Microbiology and Virology, Sant’Orsola-Malpighi Hospital, Bologna, Italy;3. Scientific Affairs, Abbott Diagnostici, Roma, Italy;1. Pediatric Clinic 1, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;2. The Pediatric Infectious Disease Unit, Soroka University Medical Center, Beer-Sheva, Israel;3. The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel;4. Molecular Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;1. Infectious Diseases Unit, Shaare Zedek Medical Center affiliated with the Hebrew University Hadassah Medical School, Jerusalem, Israel;2. Clinical Virology Unit, Hadassah Hospital, The Hebrew University Hadassah Medical School, Jerusalem, Israel;1. Department of Pathology and Laboratory Medicine, Albany Medical Center Hospital, Albany, New York, United States;2. Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, United States;3. Department of Surgery, Albany Medical College, Albany, New York, United States
Abstract:BackgroundInfection with pandemic A/H1N1/2009 influenza virus led to hospitalisation of patients not expected to be at risk of severe disease from seasonal influenza infection.ObjectivesWe sought to establish whether (i) DC maturation was compromised in patients experiencing severe pandemic influenza infection, (ii) the pandemic virus differed from seasonal influenza virus in its ability to induce DC maturation and (iii) there was an associated inability to activate memory B cells or induce antibody.Study designPeripheral blood mononuclear (PBMCs) cells were sampled from individuals with confirmed acute pandemic A/H1N1/2009 influenza infection or from healthy vaccinated controls. DCs were differentiated from the PBMC and tested for their ability to mature following stimulation with pandemic virus, seasonal H3N2 influenza virus or LPS. Serum samples from the patients were used to assess seroconversion to influenza and the levels of influenza specific memory B cells in PBMC were also determined.ResultsDCs obtained from all individuals exhibited negligible maturation marker upregulation when exposed to pandemic A/H1N1/2009 virus but showed a strong response to the seasonal H3N2 virus and LPS. Robust levels of memory B cell were obtained in both groups and patients seroconverted to the virus.ConclusionsOverall, the ability of patient's DC to mature in response to different stimuli was no different to that of control subjects DCs. Importantly, panH1N109 virus failed to induce substantial DC maturation in any individual, contrasting with seasonal virus, but this did not result in failure to mount memory B cell and antibody responses to the virus.
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