Busted! Pregnancy does not cause immunosuppression in pregnant women

One of the main hypotheses used to explain the increased risk for infection and mortality during pregnancy has been the concept of “pregnancy as an immune suppressed condition”. The “paradox of pregnancy” as a semi-allograft has been approached from the point of perspective of organ transplantation. The view of the foetus as an organ transplant, and the requirement of systemic immune suppression for the success of the transplant, led to the proposal of pregnancy as a condition of systemic immune suppression as a requirement for the success of the pregnancy. From this point of view, similarly as in immune suppressed patients, pregnancy is in a state of weak immunologic protection.

This concept has been tested for many years in animal models as well as in patients with fertility problems. Unfortunately, after almost 50 years of research following this assumption, there is a lack of evidence to support this hypothesis.

Therefore, it is important to evaluate the immunologic aspects associated with pregnancy in order to further understand the potential biological reasons associated with the risk of infection during pregnancy. One wonders why the model of transplantation may not represent the correct immunological situation of pregnancy: During transplantation there is a major influx of foreign antigens as a result of the introduction of a fully foreign organ.

Under this circumstance the host immune system acutely reacts to the foreign antigens and mounts an immunologic response to reject the source of foreign antigens. During pregnancy the process is different. Pregnancy is a slow and gradual process where paternal/foetal antigens are released in a gradual and increasing manner as the blastocyst grows into an embryo and then into a foetus. The exposure of small amounts of foreign antigens during this process may actually induce tolerance rather than rejection. Consequently, pregnancy, contrary to transplantation, does not require systemic immune suppression.

A second aspect that has been ignored for many years is the role of the placenta. Pregnant women represent an immunologically unique population because their immune system is influenced by signals originating from the placenta. The presence of the foetus and placenta alters maternal immunity and physiology to sustain and protect the pregnancy. Our researches and others as well have shown that the placenta may function as an immune modulatory organ that regulates the immune responses of cells present both at the implantation site as well as systemicallyHowever, this modulation is not suppressive, but protective.

In general, the maternal immune system is well prepared to control infections and ensure the survival of the foetus. Paradoxically, the placenta is also a target for viral infections. Recent studies suggest that although the placenta can be infected by viruses it has a unique capacity to prevent expansion of the virus and transmission to the foetus. What is not clear is the effect of a viral infection on the normal homeostasis of the placenta and its interaction with the maternal immune system. A viral infection of the placenta might affect the normal homeostasis at the implantation site, as well as the systemic immune system of the mother, which will determine the type of immune response that is elicited in the presence of normal or abnormal microorganisms.

Adapted from “Viral infections during pregnancy” by Michelle Silasi, Ingrid Cardenas, Karen Racicot, Ja-Young Kwon, Paula Aldo, and Gil Mor, Department of Obstetrics Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.

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Updated: October 4, 2020 — 2:16 pm

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