The influence of pregnancy on systemic immunity

Abstract

Adaptations in maternal systemic immunity are presumed to be responsible for observed alterations in disease susceptibility and severity as pregnancy progresses. Epidemiological evidence as well as animal studies have shown that influenza infections are more severe during the second and third trimesters of pregnancy, resulting in greater morbidity and mortality, although the reason for this is still unclear. Our laboratory has taken advantage of 20 years of experience studying the murine immune response to respiratory viruses to address questions of altered immunity during pregnancy. With clinical studies and unique animal model systems, we are working to define the mechanisms responsible for altered immune responses to influenza infection during pregnancy and what roles hormones such as estrogen or progesterone play in these alterations.

Fig. 1

Increased morbidity and mortality to influenza in pregnant women compared to the general population. Statistics were taken from refs. [–23]

Fig. 2

Model of immune alterations during pregnancy. Strengthening of immune barrier functions includes increased phagocytosis, PMN activity, serum defensins and pDCs, while adaptive immunity, including NK cell cytokine secretion, T-cell activity and possibly B-cell activity, is weakened

Fig. 3

Cytokine alterations during pregnancy. Cytokines were measured by multiplex ELISA three times during pregnancy and compared to 6th month post-partum. Data were first published in ref. [50]

Fig. 4

Experimental schema. Non-pregnant mice are implanted with hormone or placebo pellet. Five days later, mice are infected with influenza X31 or mock infected. (Top) Pregnant mice are infected with X31 on E10 (Bottom). Starting at three days post-infection, mice are analyzed for cytokine and chemokine production and cell migration