Grant: Project Grant

Immunity is altered by the requirements of pregnancy to create an environment of immune tolerance to the presence of the fetus. The major portion of pregnancy is associated with a so-called T2 immune environment at the level of the placenta. This environment prevents the fetus being recognized as a foreign entity. However, this environment is associated with worsening of many autoimmune diseases and in the severity of viral illnesses in a small fraction of pregnant women. Influenza is a frequent cause of acute asthma attacks but the effects of the pregnant state on the severity of asthma caused by influenza are not well understood. Based on experiments to date in the mouse the current proposal is addressing the role of the lining cells of the airways (epithelial cells), the macrophage (an immune cell in the lung) in resistance and susceptibility to viral replication and the links to the altered immunity of pregnancy. The importance of a subset of lymphoid cells, the group 2 innate lymphoid cells, and alveolar macrophages in determining susceptibility to influenza infection will be explored. The resistant mouse strain C57Bl/6 will be mated with Balb/C mice to create an allogeneic pregnancy with increased susceptibility to influenza, to better mimic the human condition. Having mice with the same genetic background in which susceptibility and resistance to influenza infection is pregnancy are altered by the nature of the fetus will provide valuable insights without the complication of contrasting strains of mice with differing genetic backgrounds. It is hoped that the information obtained will provide clues as to the causes of severe influenza infections in some pregnant women.