title: Severe influenza A(H1N1)pdm09 infection induces thymic atrophy through activating innate CD8(+)CD44(hi) T cells by upregulating IFN-γ.
abstract: Thymic atrophy has been described as a consequence of infection by several pathogens including highly pathogenic avian influenza virus and is induced through diverse mechanisms. However, whether influenza A(H1N1)pdm09 infection induces thymic atrophy and the mechanisms underlying this process have not been completely elucidated. Our results show that severe infection of influenza A(H1N1)pdm09 led to progressive thymic atrophy and CD4+ CD8+ double-positive (DP) T-cells depletion due to apoptosis. The viruses were present in thymus, where they activated thymic innate CD8(+)CD44(hi) single-positive (SP) thymocytes to secrete a large amount of IFN-γ. Milder thymic atrophy was observed in innate CD8+ T-cell-deficient mice (C57BL/6J). Neutralization of IFN-γ could significantly rescue the atrophy, but peramivir treatment did not significantly alleviate thymic atrophy. In this study, we demonstrated that thymic innate CD8(+)CD44(hi) SP T-cells have critical roles in influenza A(H1N1)pdm09 infection-induced thymic atrophy through secreting IFN-γ. This exceptional mechanism might serve as a target for the prevention and treatment of thymic atrophy induced by influenza A(H1N1)pdm09.
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Deng
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Wen
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Bao
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: An
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Cao
authors.affiliation: 1] Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China [2] Department of Respiratory Medicine, Capital Medical University, Beijing, China [3] Beijing Institute of Respiratory Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing, China [4] Beijing Institute of Respiratory Medicine, Beijing Hospital, Ministry of Heath, P. R. China, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D001284:Atrophy; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D054884:Host-Pathogen Interactions; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007113:Immunity, Innate / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D012720:Severity of Illness Index; D015398:Signal Transduction; D013045:Species Specificity; D060168:Thymocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D007371:Interferon-gamma