Pregnant women infected with pandemic influenza A(H1N1)pdm09 virus showed differential immune response correlated with disease severity |
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Affiliation: | 1. National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS “Carlos G. Malbrán”, Buenos Aires, Argentina;2. Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA CONICET), Argentina;1. Department of Radiation Oncology, Cancer Center, First People''s Hospital of Foshan, Foshan 528000, Guangdong Province, PR China;2. Department of Medical Oncology, Cancer Center, First People''s Hospital of Foshan, Foshan 528000, Guangdong Province, PR China;3. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;4. Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, PR China;5. Experimental Therapeutics Academic Program and Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA;6. Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, PR China;1. Department of Clinical and Experimental Medicine, University of Messina, Italy;2. Neonatal Intensive Care Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Italy;3. Obstetrics and Gynecology Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Italy;4. Unit of Paediatric Surgery, Department of Human Pathology in Adult and Developmental Age, University of Messina, Messina, Italy;5. Department of Economical, Business and Environmental Sciences and Quantitative Methods, University of Messina, Italy;6. Unit of Paediatric Genetics and Immunology, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Italy;7. Department of Pediatrics, University of Siena, Italy;8. Department of Cell Systems and Anatomy, The University of Texas Health Science Center, San Antonio, USA;1. ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA;2. Abbott Molecular Inc., 1350 E. Touhy Avenue, Des Plaines, IL 60018, USA;3. University of Utah Department of Pathology, 15 North Medical Drive East, Salt Lake City, UT 84112, USA;1. Fundação Oswaldo Cruz, Laboratório de Desenvolvimento Tecnológico em Virologia, Rio de Janeiro, Brazil;2. Institut für Virologie, Universitätsklinikum Ulm, Ulm, Germany;3. Hospital Geral de Bonsucesso, Rio de Janeiro, Brazil;4. Fundação Oswaldo Cruz, Laboratório de Patologia, Rio de Janeiro, Brazil;5. Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Hamburg, Germany;1. Austrian Red Cross, Blood Service for Vienna, Lower Austria and Burgenland, 1040 Vienna, Austria;2. German Red Cross, Blood Service for Baden-Württemberg-Hessen, Frankfurt, Germany;3. Department of Virology, Medical University of Vienna, Vienna, Austria;4. Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Hamburg, Germany;5. German Centre for Infection Research (DZIF), partner site Hamburg-Luebeck-Borstel, Hamburg, Germany;1. Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;2. National Centre for Epidemiology, Surveillance and Health Promotion (CNESPS), Istituto Superiore di Sanità (ISS), Via Giano della Bella 34, 00162 Rome, Italy |
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Abstract: | BackgroundDuring pregnancy, immunological and hormonal alterations place women at increased risk for influenza-related severe illnesses including hospitalization and death. Although A(H1N1) pdm09 infection resulted in increased disease severity in pregnant women, the precise mechanisms responsible for this risk have yet to be established.ObjectivesThe present study was aimed to investigate the role of host chemokines and cytokine profiles in A(H1N1) pdm09 infection regarding disease severity in pregnant women.Study designThis retrospective survey examined 41 pregnant women with confirmed A(H1N1) pdm09 infection. Of them, 12 died (D), 29 survived (S), and 17 remained uninfected and served as controls (C). Antiviral response was evaluated for IFN-β expression and gene expression profiles of cytokines (TNF-α, IL-6, IL-12, TGF-β) and chemokines (IL-8, RANTES, MCP-1, IP-10), and the viral Matrix (M1) gene was quantified and normalized using the housekeeping gene product β-actin mRNA.ResultsHigher IL-8 and TNF-α mRNA expression were found in D and S compared with C, while IL-6 showed higher expression in D. Interestingly, these results were associated with a decrease in the anti-inflammatory response of TGF-β mRNA and IFN-β. These alterations would lead to an imbalance in the immune response of those patients.ConclusionsPregnancy-related reductions in IFN-β and TGF-β expression levels and elevated levels of pro-inflammatory cytokines could explain the increased severity of infection and death of pregnant women. These findings may help improve the understanding of the high susceptibility and disease severity to influenza virus infection during pregnancy. |
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Keywords: | Influenza virus A(H1N1)pdm09 Cytokines Chemokines Pregnant women |
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