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J Immunol. 2017 Mar 15;198(6):2479-2488. doi: 10.4049/jimmunol.1601855. Epub 2017 Feb 8.

Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy.

Author information

1
Division of Translational Medicine, Department of Systems Biology, Sidra Medical and Research Center, 26999 Doha, Qatar.
2
Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
3
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
4
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
5
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305.
6
Baylor Scott and White Health, Dallas, TX 75246.
7
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032.
8
Benaroya Research Institute at Virginia Mason, Seattle, WA 98101.
9
Institute for Immunity, Transplantation of Infection, Stanford University School of Medicine, Stanford, CA 94305; and.
10
Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305.
11
Division of Translational Medicine, Department of Systems Biology, Sidra Medical and Research Center, 26999 Doha, Qatar; furmand@stanford.edu.

Abstract

Despite clear differences in immune system responses and in the prevalence of autoimmune diseases between males and females, there is little understanding of the processes involved. In this study, we identified a gene signature of immature-like neutrophils, characterized by the overexpression of genes encoding for several granule-containing proteins, which was found at higher levels (up to 3-fold) in young (20-30 y old) but not older (60 to >89 y old) males compared with females. Functional and phenotypic characterization of peripheral blood neutrophils revealed more mature and responsive neutrophils in young females, which also exhibited an elevated capacity in neutrophil extracellular trap formation at baseline and upon microbial or sterile autoimmune stimuli. The expression levels of the immature-like neutrophil signature increased linearly with pregnancy, an immune state of increased susceptibility to certain infections. Using mass cytometry, we also find increased frequencies of immature forms of neutrophils in the blood of women during late pregnancy. Thus, our findings show novel sex differences in innate immunity and identify a common neutrophil signature in males and in pregnant women.

PMID:
28179497
PMCID:
PMC5337813
DOI:
10.4049/jimmunol.1601855
[Indexed for MEDLINE]
Free PMC Article

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