^{Department of Obstetrics and Gynecology, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford University, Palo Alto, CA, United States}

^{Department of Microbiology and Immunology, Stanford University, Palo Alto, CA, United States}

^{Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, United States}

^{Chan Zuckerberg Biohub, San Francisco, CA, United States}

Edited by: Henrik Mei, Deutsches Rheuma-Forschungszentrum (DRFZ), Germany

Reviewed by: Kanutte Huse, Oslo University Hospital, Norway; Quirin Hammer, Karolinska Institute (KI), Sweden; Bertram Bengsch, Freiburg University Medical Center, Germany

*Correspondence: Mathieu Le Gars ude.drofnats@hsilbc

Catherine A. Blish moc.liamg@1sragel.ueihtam

This article was submitted to NK and Innate Lymphoid Cell Biology, a section of the journal Frontiers in Immunology

Edited by: Henrik Mei, Deutsches Rheuma-Forschungszentrum (DRFZ), Germany

Reviewed by: Kanutte Huse, Oslo University Hospital, Norway; Quirin Hammer, Karolinska Institute (KI), Sweden; Bertram Bengsch, Freiburg University Medical Center, Germany

Received 2019 May 23; Accepted 2019 Oct 3.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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, CD56^{, and CD56}^{NK cells, to respond to influenza-virus infected cells and tumor cells. During pregnancy, CD56}^{and CD56}^{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 CD56}^{and CD56}^{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 CD56}^{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.}

Keywords: NK cells, pregnancy, influenza virus, cancer cells, NK repertoire

Abstract

Acknowledgments

We thank our study volunteers for their participation, Sally Mackey for regulatory and data management, Sue Swope for consenting and conducting study visits, and the staff of the Stanford Vaccine Program for overall study coordination. This manuscript has been released as a Pre-Print at Biorxiv (62).

Acknowledgments

Footnotes

Funding. This was supported by an Elizabeth and Russell Siegelman Fellowship in Infectious Diseases from the Stanford Child Health Research Institute (CHRI) to AK, a Stanford CHRI post-doctoral fellowship to ML, the CHRI – Stanford Clinical and Translational Science Award grant number UL1 TR000093 (AK), a National Institutes of Health (NIH) Training Grant: Viral Infections in Children T32 AI78896-05 (AK), a Smith Family Stanford Graduate Fellowship (NB), Ruth L. Kirschstein NRSA 1F31HD089675 (NB), a Clinical Scientist Development Award #2013099 from the Doris Duke Charitable Foundation (CB), the McCormick Faculty Award (CB), Tasha and John Morgridge Endowed Faculty Scholar in Pediatric Translational Medicine from Stanford CHRI and Stanford University School of Medicine (CB), a NIH Director's New Innovator Award DP2AI112193 (CB), an Infrastructure and Opportunity Fund (CB) as part of the Stanford Human Immunology Project Consortium (HIPC) Grant U19AI090019 (MD), and an investigator award from the Chan Zuckerberg Biohub (CB). Clinical cohorts were supported by NIH U19AI057229 (MD) and an NIH/NCRR CTSA award UL1 RR025744 (H. Greenberg).

Footnotes

Click here for additional data file.^{(18K, DOCX)}Click here for additional data file.^{(5.8M, PDF)}

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