Pregnancy-Induced Alterations in NK Cell Phenotype and Function

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.

Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women

“…These changes alter immunity to a wide range of pathogens, including influenza virus, which significantly drives morbidity and mortality in the pregnant population. In general, women have enhanced innate NK cell, monocyte, and dendritic cell responses to influenza virus (10,11,13,58), yet there are also reports that there is reduced IFN-alpha and IFN-lambda production in response to influenza (59). In general, adaptive immune function is thought to be suppressed during pregnancy, though pregnant women respond adequately to influenza immunization (9,60).…”

Maternal Immunological Adaptation During Normal Pregnancy

“…The augmented inflammatory NK cell capacity during pregnancy is further supported by studies showing increased expression of the activation marker CD69 on CD4 neg iNKT cells as pregnancy progresses ( 136 ). Similarly, expression of the degranulation marker LAMP-1 (CD107a) on CD56 dim cells after PMA-ionomycin stimulation and baseline levels of the cytotoxic markers NKp46 (CD335) and CD38 are increased in the third trimester compared to non-pregnant women ( 101 , 137 , 145 ). Additionally, in vitro NK cell responses to influenza-infected or cancerous cells is higher in pregnancy ( 145 ).…”

“…Similarly, expression of the degranulation marker LAMP-1 (CD107a) on CD56 dim cells after PMA-ionomycin stimulation and baseline levels of the cytotoxic markers NKp46 (CD335) and CD38 are increased in the third trimester compared to non-pregnant women ( 101 , 137 , 145 ). Additionally, in vitro NK cell responses to influenza-infected or cancerous cells is higher in pregnancy ( 145 ). Together, this indicates elevated baseline activity and heightened potential to upregulate pro-inflammatory responses, underlining increased innate immunity during pregnancy.…”

Sharing Knowledge With Young and Established Students of Immunology by the Neapolitan Gulf at the Ruggero Ceppellini Advanced School

“…Adding to the complexity of the maternal-fetal interactions is the heterogeneity of immune cells, revealed recently by singe-cell RNA-sequencing (21) and mass cytometry (22). Mass cytometry has been applied to study also the fluctuations in blood immune cells throughout pregnancy (23,24). Multiple populations of innate lymphoid cells (9,21,25), regulatory T cells (26), and macrophages (27) compose the diverse immune cell landscape operating at the maternalfetal interface, which varies during the stages of pregnancy and it is therefore difficult to decipher precisely.…”