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

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 gen...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2017-03, Vol.198 (6), p.2479-2488
Main Authors: Blazkova, Jana, Gupta, Sarthak, Liu, Yudong, Gaudilliere, Brice, Ganio, Edward A, Bolen, Christopher R, Saar-Dover, Ron, Fragiadakis, Gabriela K, Angst, Martin S, Hasni, Sarfaraz, Aghaeepour, Nima, Stevenson, David, Baldwin, Nicole, Anguiano, Esperanza, Chaussabel, Damien, Altman, Matthew C, Kaplan, Mariana J, Davis, Mark M, Furman, David
Format: Article
Language:English
Subjects:
Adult
Age Factors
Aged
Aged, 80 and over
Autoimmune diseases
Blood Cells - physiology
Cytometry
Female
Females
Granulocyte Precursor Cells - physiology
Humans
Immune system
Innate immunity
Leukocytes (neutrophilic)
Male
Males
Middle Aged
Neutrophils
Neutrophils - physiology
Peripheral blood
Pregnancy
Proteins
Sex
Sex differences
Systems analysis
Systems Immunology
Transcriptome
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1601855