Pregnancy-Induced Alterations in NK Cell Phenotype and Function.

Mathieu Le Gars,Alexander W Kay,Mark M Davis,Catherine A Blish,Lindsay Moore,Elina Starosvetsky,Gary E Swan,Nicholas L Bayless,Purvesh Khatri,Natali Aziz,Susan Holmes,Christof Seiler,Shai S Shen-Orr,Cornelia L Dekker

doi:10.3389/fimmu.2019.02469

Abstract

Pregnant women are particularly susceptible to complications of influenza A virus infection, which may result from pregnancy-induced changes in the function of immune cells, including natural killer (NK) cells. To better understand NK cell function during pregnancy, we assessed the ability of the two main subsets of NK cells, CD56dim, and CD56bright NK cells, to respond to influenza-virus infected cells and tumor cells. During pregnancy, CD56dim and CD56bright NK cells displayed enhanced functional responses to both infected and tumor cells, with increased expression of degranulation markers and elevated frequency of NK cells producing IFN-γ. To better understand the mechanisms driving this enhanced function, we profiled CD56dim and CD56bright NK cells from pregnant and non-pregnant women using mass cytometry. NK cells from pregnant women displayed significantly increased expression of several functional and activation markers such as CD38 on both subsets and NKp46 on CD56dim NK cells. NK cells also displayed diminished expression of the chemokine receptor CXCR3 during pregnancy. Overall, these data demonstrate that functional and phenotypic shifts occur in NK cells during pregnancy that can influence the magnitude of the immune response to both infections and tumors.

Highlights

During pregnancy, the immune system has to finely balance its activity in order to tolerate the semiallogeneic fetus, while maintaining the ability to fight microbial challenges [1,2,3,4]
The maternal immune system is engaged in a fine balance: tolerance is required to preserve the fetus while defenses must be maintained to protect mother and baby from microbial challenges
natural killer (NK) cells from pregnant women display diminished responses to stimulation with cytokines and phorbol-myristate acetate and ionomycin, yet NK cell responses to influenza-infected cells are enhanced [12,13,14, 32]. We show that both CD56dim and CD56bright NK cell subsets have enhanced responses to both the influenza virus and to cancer cells, indicating a cell-intrinsic enhancement in their response to threats

Summary

Introduction

The immune system has to finely balance its activity in order to tolerate the semiallogeneic fetus, while maintaining the ability to fight microbial challenges [1,2,3,4]. NK cells reduced influenza virus burden and promoted clearance of the virus in mice deficient in NKp46, a major NK cell receptor thought to play a role in influenza recognition [17], suggesting that NK cells may contribute to protection from influenza. Controversy remains as another mouse strain deficient in NKp46 expression is resistant to viral infection [18]. This NK cell recruitment correlated with severity of lung inflammation and poor patient outcome, but the causality in the relation between infiltration of NK cells and viral clearance and pathogenesis is unproven

Objectives

Methods

Results

Conclusion