Does placental MDSC-mediated modulation of arginine levels help protect the foetus from auxotrophic pathogens?

Abstract

Myeloid-derived suppressor cells (MDSCs) are immunosuppressive precursors of dendritic cells, macrophages and granulocytes. MDSCs normally quickly differentiate, but have elevated levels in chronic infection and cancer, where they help tumours evade the immune system through induction of T-cell dysfunction. MDSC levels are also raised in pregnancy, and in the neonate. During pregnancy they may help to prevent maternal rejection of the semiallogenic foetus. In the immediate postnatal period they may aid in allowing tolerance of gut microbiological colonisation and non-pathological environmental antigens. MDSC immunosuppression involves reduction of arginine levels, which leads to downregulation of T-cell receptor (TCR) and cell proliferation. Arginine is also involved in replication, and virulence of a variety of viruses and bacteria, including Hepatitis D, HIV-1, Herpes simplex, Adenovirus, Staphylococci, Neisseria gonorrhoea, Escherichia coli, and Streptococci. Given the above it could be hypothesised that MDSC-mediated reduction in levels during pregnancy and the perinatal period is not just a by-product of T-cell immunosuppression, but potentially a primitive part of the innate immune system. Increased arginase activity would therefore serve a dual purpose, inhibiting the adaptive immune system whilst also providing a degree of protection against infection by arginine auxotrophic pathogens.

Keywords:

• Myeloid derived suppressor cells
• arginine
• arginase

Acknowledgements

I would like to thank Dr Francis Mussai (Clinical Senior Lecturer in Paediatric Oncology, University of Birmingham, UK) and Dr David Lissauer (Clinical Lecturer in Obstetrics and Gynaecology, University of Birmingham, UK) for their helpful discussions in formulating this hypothesis.

Disclosure statement

The authors report no conflicts of interest.