Prolonged activation of innate antiviral gene signature after childbirth is determined by IFNL3 genotype.
Maternal innate and adaptive immune responses are modulated during pregnancy to concurrently defend against infection and tolerate the semiallogeneic fetus. The restoration of these systems after childbirth is poorly understood. We reasoned that enhanced innate immune activation may extend beyond gestation while adaptive immunity recovers. To test this hypothesis, the transcriptional profiles of total peripheral blood mononuclear cells following delivery in healthy women were compared with those of nonpregnant control subjects. Interestingly, interferon-stimulated genes (ISGs) encoding proteins such as IFIT1, IFIT2, and IFIT3, as well as signaling proteins such as STAT1, STAT2, and MAVS, were enriched postpartum. Antiviral genes were primarily expressed in CD14(+) cells and could be stratified according to genetic variation at the interferon-λ3 gene (IFNL3, also named IL28B) SNP rs12979860. Antiviral gene expression was sustained beyond 6 mo following delivery in mothers with a CT or TT genotype, but resembled baseline nonpregnant control levels following delivery in mothers with a CC genotype. CT and TT IFNL3 genotypes have been associated with persistent elevated ISG expression in individuals chronically infected with hepatitis C virus. Together, these data suggest that postpartum, the normalization of the physiological rheostat controlling IFN signaling depends on IFNL3 genotype.
Emory Vaccine Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329;
Aryn A
AA
Price
Emory Vaccine Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329;
Dana
D
Tedesco
Department of Obstetrics and Gynecology, The Ohio State University School of Medicine, Columbus, OH 43205;
Mona R
MR
Prasad
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322;
Kimberly A
KA
Workowski
The Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205; Department of Pediatrics, The Ohio State University School of Medicine, Columbus, OH, 43205;
Christopher M
CM
Walker
Emory Vaccine Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; Department of Pediatrics and Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322;
Mehul S
MS
Suthar
The Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205; Department of Pediatrics, The Ohio State University School of Medicine, Columbus, OH, 43205; jonathan.honegger@nationwidechildrens.org arash.grakoui@emory.edu.
Jonathan R
0000-0002-3181-0554
JR
Honegger
Emory Vaccine Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30329 jonathan.honegger@nationwidechildrens.org arash.grakoui@emory.edu.
Arash
A
Grakoui
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D033261:Maternal-Fetal Relations; D020641:Polymorphism, Single Nucleotide; D049590:Postpartum Period; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C484290:IFIT1 protein, human; C484289:IFIT2 protein, human; C116468:IFIT3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors; D011506:Proteins; D016601:RNA-Binding Proteins
CD14; antiviral genes; innate immunity; interferon; postpartum