Pregnancy Downregulates Plasmablast Metabolic Gene Expression Following Influenza without Altering Long-Term Antibody Function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA649557 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12345910.fastq.gz | Fastqsanger.gz | |||
| SRR12345911.fastq.gz | Fastqsanger.gz | |||
| SRR12345912.fastq.gz | Fastqsanger.gz | |||
| SRR12345913.fastq.gz | Fastqsanger.gz | |||
| SRR12345914.fastq.gz | Fastqsanger.gz |
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Project description:The normal response to influenza A infection is to remain asymptomatic; indeed, a study of volunteers who tested positive for antibodies against 2009 H1N1 revealed that a majority did not experience symptoms. However, studies of influenza pandemics since the 20th century, and to a lesser degree seasonal flu, suggest that pregnancy increases influenza-associated morbidity and mortality. The confounding effect of pregnancy has been well established to adversely alter the clinical course of influenza, with short term complications to mother and baby apparent, and long-term consequences to the fetus hypothesized. However, how the condition of pregnancy impacts long-term maternal anti-influenza immunity remains contentious; while vaccination studies suggest humoral responses sufficient for protection, published research on adaptive immune responses against influenza formed during pregnancy is limited. This study expands upon published work from our lab and others by comprehensively examining compartmental and systemic changes following pandemic A/California/07/2009 influenza infection. Previously, we linked seasonal influenza infection to clinical observations of adverse outcomes in pregnancy, enhanced lung and placental histopathology, and reduced control of viral replication in lungs of infected pregnant mothers. Here, we observe that the results of a lower infectious dose of pandemic influenza are similar to that of seasonal influenza. Importantly, we expand upon work which suggests infection during pregnancy may also affect humoral immunity. Our observations of reduced early antibody hemagglutinin inhibition and virus neutralization which resolved within 8 weeks of delivery demonstrate that influenza infection impacts antibody maturation mechanisms without alterations to B cell frequency or antibody secretion. This hypothesis is further supported by plasmablast transcriptional data, which demonstrates downregulated B cell metabolism and post-translational modification systems only among pregnant animals. These findings corroborate a link between adverse pregnancy outcomes and severe pathology observed during influenza infection, and propose resolving humoral deficiencies following influenza infection confounded by pregnancy. Additional studies are required to specify the involvement of plasmablast metabolism with early humoral immunity abnormalities to best guide vaccination strategies and improve our understanding of the immunological consequences of pregnancy.
2020-07-30 | GSE155388 | GEO
Project description:While the majority of influenza-infected individuals show no or mild symptomatology, pregnant women are at higher risk of complications and infection-associated mortality. Although enhanced lung pathology and dysregulated hormones are thought to underlie adverse pregnancy outcomes following influenza infection, how pregnancy confounds long-term maternal anti-influenza immunity remains to be elucidated. Previously, we linked seasonal influenza infection to clinical observations of adverse pregnancy outcomes, enhanced lung and placental histopathology, and reduced control of viral replication in lungs of infected pregnant mothers. Here, we expand on this work and demonstrate that lower infectious doses of the pandemic A/California/07/2009 influenza virus generated adverse gestational outcomes similar to higher doses of seasonal viruses. Mice infected during pregnancy demonstrated lower hemagglutination inhibition and neutralizing antibody titers than non-pregnant animals until 63 days post infection. These differences in humoral immunity suggest that pregnancy impacts antibody maturation mechanisms without alterations to B cell frequency or antibody secretion. This is further supported by transcriptional analysis of plasmablasts, which demonstrate downregulated B cell metabolism and post-translational modification systems only among pregnant animals. In sum, these findings corroborate a link between adverse pregnancy outcomes and severe pathology observed during pandemic influenza infection. Furthermore, our data propose that pregnancy directly confounds humoral responses following influenza infection which resolves post-partem. Additional studies are required to specify the involvement of plasmablast metabolism with early humoral immunity abnormalities to best guide vaccination strategies and improve our understanding of the immunological consequences of pregnancy.
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Project description:To study the plasmablast response to influenza vaccines We want to test and see that LAIV, TIV and ID TIV induced different plasmablast response We take peripheral plasmablast and test its response to influenza vaccines at day 7 after vaccination. This array data set is for day 0 (before vaccines)
2016-07-01 | E-GEOD-62110 | biostudies-arrayexpress
Project description:To study the plasmablast response to influenza vaccines We want to test and see that LAIV, TIV and ID TIV induced different plasmablast response
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Project description:To study the plasmablast response to influenza vaccines We want to test and see that LAIV, TIV and ID TIV induced different plasmablast response
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Project description:Antibody-mediated immunity is initiated by B cell interactions with cognate antigen, followed by differentiation into multiple cell subsets, including plasmablast, memory, and germinal center (GC) cells. B cell differentiation trajectories are determined by specific transcription factors, yet very few mechanisms that determine B cell fate at the early stage of the response have been described. Here, we report an epigenetic mechanism that specifically suppresses the plasmablast genetic program and promotes GC B cell fate commitment. Single-cell RNA-seq analysis of antigen-specific B cells revealed activated B cell precursors at the pre-GC stage that express high levels of RNA binding proteins, including YTHDF2, which enhances the decay of methylated transcripts. Ythdf2-deficient B cells exhibited intact proliferation and upregulation of early activation markers in response to antigenic stimulation, whereas differentiation into GC B cells was blocked. Mechanistically, B cells required YTHDF2 to attenuate the plasmablast genetic program during GC seeding, and key transcripts of plasmablast-related genes, including Irf4 and Xbp1, were methylated and bound by YTHDF2. Modulation of YTHDF2-dependent gene expression by YTHDF1 and YTHDF3 was less pronounced, and no functional redundancy of these paralogs in GC seeding was observed. Collectively, this study reveals a novel epigenetic mechanism that specifically directs appropriate B cell fate commitment through post-transcriptional suppression of gene expression.
2022-04-24 | GSE189819 | GEO
Project description:LSD1 regulates plasmablast chromatin accessibility
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Project description:LSD1 regulates the plasmablast transcriptome
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Project description:LSD1 regulates the plasmablast transcriptome
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Project description:Inactivated influenza vaccine (IIV) is recommended during pregnancy to prevent influenza infection and its complications in pregnant women and their infants. However, the extent to which pregnancy modifies the antibody response to vaccination remains unclear, and prior studies have focused primarily on hemagglutinin inhibition (HI) titers. A more comprehensive understanding of how pregnancy modifies the humoral immune response to influenza vaccination will aid in maximizing vaccine efficacy.Healthy pregnant women and control women were studied prior to, 7 days after, and 28 days after vaccination with IIV. HI titers, microneutralization (MN) titers, and the frequency of circulating plasmablasts were evaluated in pregnant versus control women.Pregnant women and control women mount similarly robust serologic immune responses to IIV, with no significant differences for any influenza strain in postvaccination geometric mean HI or MN titers. HI and MN titers correlate, though MN titers demonstrate more robust changes pre- versus postvaccination. The induction of circulating plasmablasts is increased in pregnant women versus controls (median fold-change 2.60 vs 1.49 [interquartile range, 0.94-7.53 vs 0.63-2.67]; P = .03).Pregnant women do not have impaired humoral immune responses to IIV and may have increased circulating plasmablast production compared to control women.
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