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 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.
Division of Translational Medicine, Department of Systems Biology, Sidra Medical and Research Center, 26999 Doha, Qatar.
Jana
J
Blazkova
Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
Sarthak
S
Gupta
Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
Yudong
Y
Liu
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
Brice
0000-0002-3475-5706
B
Gaudilliere
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
Edward A
0000-0002-1088-0377
EA
Ganio
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
Christopher R
CR
Bolen
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
Ron
R
Saar-Dover
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
Gabriela K
0000-0001-9703-2591
GK
Fragiadakis
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
Martin S
MS
Angst
Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
Sarfaraz
0000-0002-4164-8837
S
Hasni
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
Nima
N
Aghaeepour
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305.
David
D
Stevenson
Baylor Scott and White Health, Dallas, TX 75246.
Nicole
0000-0002-4196-3554
N
Baldwin
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032.
Esperanza
E
Anguiano
Division of Translational Medicine, Department of Systems Biology, Sidra Medical and Research Center, 26999 Doha, Qatar.
Damien
D
Chaussabel
Benaroya Research Institute at Virginia Mason, Seattle, WA 98101.
Matthew C
MC
Altman
Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
Mariana J
MJ
Kaplan
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.|Institute for Immunity, Transplantation of Infection, Stanford University School of Medicine, Stanford, CA 94305; and.|Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305.
Mark M
MM
Davis
Division of Translational Medicine, Department of Systems Biology, Sidra Medical and Research Center, 26999 Doha, Qatar; furmand@stanford.edu.|Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.|Institute for Immunity, Transplantation of Infection, Stanford University School of Medicine, Stanford, CA 94305; and.
David
D
Furman
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001773:Blood Cells / Q000502:physiology*; D005260:Female; D042381:Granulocyte Precursor Cells / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D011247:Pregnancy; D012723:Sex; D059467:Transcriptome; D055815:Young Adult