Rôle de l'hémostase dans l'inflammation induite par les virus influenza A

Abstract : Influenza is an acute respiratory disease caused by infection with influenza virus and is a major public health problem. A better understanding of the interaction between influenza virus and host allow us to better understand the pathophysiology of influenza infection, and thus, ultimately, to better protect themselves against the disease. Morbidity and mortality caused by severe influenza infections are associated with dysregulation of the immune response in the lung. This deleterious inflammation is the cause of lung collateral damage, causing a decrease in the patient's breathing capacity. Although the mechanisms involved are not fully understood, recent studies point to a central role of endothelial cells in the deregulation of the host response to influenza infection. During endothelium aggression, the physiological process of hemostasis (platelet activation, coagulation and fibrinolysis) is activated in order to allow wound healing and to maintain the integrity of blood vessels. In many inflammatory diseases, the only dysregulation of hemostasis is directly linked to a deleterious inflammatory response. During my thesis, we hypothesized that hemostasis could be the cause of the inflammatory dysregulation during influenza infections. Our data show the role of two factors strongly involved in hemostasis: the thrombin activated receptor, PAR-1 (protease activated receptor 1) and plasminogen, in the deleterious lung inflammation and in the pathogenicity of influenza virus. Besides the role of hemostasis, we have also been able to show that the influenza virus incorporates cellular proteins in the viral envelope, allowing it to evade the immune system, which could also contribute to the deregulation of the host response. All the results obtained allowed to better understand the mechanisms involved in immune response dysregulation during influenza infection and suggest new therapeutic targets to fight against the disease
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Fatma Berri. Rôle de l'hémostase dans l'inflammation induite par les virus influenza A. Immunologie. Université Claude Bernard - Lyon I, 2014. Français. ⟨NNT : 2014LYO10351⟩. ⟨tel-01128271⟩

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