Influenza is a common respiratory infection that affects between 5-10% of the adult worldwide population annually. A significant risk factor for increased susceptibility to influenza infection, discovered almost a century ago, is pregnancy. Furthermore, pregnant women are more prone to developing worse symptoms compared with the general population. Influenza infection during late pregnancy can have severe health complications for both the mother (hospitalization and even death) and the fetus (low birthweight, preterm delivery and stillbirth). However, little is known in regards to the immune response occurring in the gestational tissues during influenza infection that lead to pregnancy complications. Mapping the underlying mechanisms will progress our understanding of potential treatment strategies that could be used to protect against influenza-related adverse pregnancy outcomes. For this purpose, we have developed an experimental model of influenza A infection during pregnancy.
BALB/c mice were time-mated and infected with a low dose of H1N1 influenza A virus (mouse adapted PR8 strain) at gestational day (GD) 9.5 (corresponding to mid-late gestation). The progression of the disease was assessed daily post infection by measuring body weight and scoring disease severity. In pregnant mice, influenza infection resulted in reduced weight gain starting at day 6 post-infection (GD15.5) compared to healthy pregnant animals. Furthermore, the average pup weight at GD17.5 was significantly lower in influenza-infected animals than in non-infected pregnant mice.
The immune response in gestational tissues (uterus, placenta and decidua) was compared between pregnant mice infected or not with influenza virus at GD17.5. Using 13-parameter flow cytometry, we were able to identify modulation of immune cell populations (including dendritic cells, macrophages and lymphocytes) in gestational tissues during respiratory viral infection.