scholarly journals Loss of circadian protection against influenza infection in adult mice exposed to hyperoxia as neonates

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yasmine Issah ◽  
Amruta Naik ◽  
Soon Y Tang ◽  
Kaitlyn Forrest ◽  
Thomas G Brooks ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Early Life ◽  
Influenza A ◽  
Negative Impact ◽  
Influenza Infection ◽  
Time Of Day ◽  
Alveolar Type ◽  
Neonatal Hyperoxia ◽  
Early Life Exposures

Adverse early-life exposures have a lasting negative impact on health. Neonatal hyperoxia that is a risk factor for bronchopulmonary dysplasia confers susceptibility to influenza A virus (IAV) infection later in life. Given our previous findings that the circadian clock protects against IAV, we asked if the long-term impact of neonatal hyperoxia vis-à-vis IAV infection includes circadian disruption. Here, we show that neonatal hyperoxia abolishes the clock-mediated time of day protection from IAV in mice, independent of viral burden through host tolerance pathways. We discovered that the lung intrinsic clock (and not the central or immune clocks) mediated this dysregulation. Loss of circadian protein, Bmal1, in alveolar type 2 (AT2) cells recapitulates the increased mortality, loss of temporal gating, and other key features of hyperoxia-exposed animals. Our data suggest a novel role for the circadian clock in AT2 cells in mediating long-term effects of early-life exposures to the lungs.

scholarly journals Loss of Circadian Protection in Adults Exposed to Neonatal Hyperoxia

2020 ◽  
Author(s):  
Yasmine Issah ◽  
Amruta Naik ◽  
Soon Y Tang ◽  
Kaitlyn Forrest ◽  
Thomas G Brooke ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Early Life ◽  
Influenza A ◽  
Negative Impact ◽  
Influenza Infection ◽  
Time Of Day ◽  
Long Term Effects ◽  
Neonatal Hyperoxia ◽  
Early Life Exposures

AbstractAdverse early life exposures having a lasting negative impact on health. For examples, neonatal hyperoxia which is a risk factor for chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD) confers susceptibility to respiratory infections like Influenza A (IAV) later in life. Given our previous findings that the circadian clock exerts a protective effect on injury from IAV, we asked if the long-term impact of neonatal hyperoxia includes disruption of circadian rhythms. We show here that neonatal hyperoxia abolishes the circadian clock mediated time of day protection from IAV, not through the regulation of viral burden, but through host tolerance pathways. We further discovered that that this dysregulation is mediated through the intrinsic clock in the lung, rather than through central or immune system clocks. Loss of circadian protein, Bmal1, in AT2 cells of the lung recapitulates the increased mortality, loss of temporal gating and other key features of hyperoxia-exposed animals. Taken together, our data suggest a novel role for the circadian clock in AT2 clock in mediating long-term effects of early life exposures to the lungs.Brief SummaryNeonatal hyperoxia abrogates the circadian protection from Influenza infection in recovered adults.

scholarly journals A Systematic Review of Longitudinal Cohort Studies Examining Unintentional Injury in Young Children

2018 ◽  
Vol 5 ◽  
pp. 2333794X1877421 ◽  
Author(s):  
Mark R. Zonfrillo ◽  
James G. Linakis ◽  
Eunice S. Yang ◽  
Michael J. Mello
Keyword(s):  
Systematic Review ◽  
Young Children ◽  
Cohort Studies ◽  
Early Life ◽  
Unintentional Injury ◽  
Population Based ◽  
Incidence Rates ◽  
Early Life Exposures ◽  
Injury Definition

Objective. Injury is the leading cause of death and long-term disability in children. Longitudinal cohorts are designed to follow subjects longitudinally in order to determine if early-life exposures are related to certain health outcomes. Methods. We conducted a systematic review to identify studies of children from birth through 5 years who were followed longitudinally with unintentional injury as an outcome of interest. Results. Of the 1892 unique references based on the search criteria, 12 (published between 2000 and 2013) were included. The studies varied on the population of focus, injury definition, and incidence rates. Existing studies that longitudinally follow children aged 0 to 5 years are limited in number, scope, and generalizability. Conclusions. Further study using population-based longitudinal cohorts is necessary to more comprehensively estimate incidence of injury in young children.

scholarly journals OVX836 Heptameric Nucleoprotein Vaccine Generates Lung Tissue-Resident Memory CD8+ T-Cells for Cross-Protection Against Influenza

2021 ◽  
Vol 12 ◽  
Author(s):  
Judith Del Campo ◽  
Julien Bouley ◽  
Marion Chevandier ◽  
Carine Rousset ◽  
Marjorie Haller ◽  
...  
Keyword(s):  
T Cells ◽  
Recombinant Protein ◽  
Dna Sequence ◽  
Cd8 T Cells ◽  
Influenza A ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
Protein Vaccine ◽  
Memory Cd8 T Cells

Tissue-resident memory (TRM) CD8+ T-cells play a crucial role in the protection against influenza infection but remain difficult to elicit using recombinant protein vaccines. OVX836 is a recombinant protein vaccine, obtained by the fusion of the DNA sequence of the influenza A nucleoprotein (NP) to the DNA sequence of the OVX313 heptamerization domain. We previously demonstrated that OVX836 provides broad-spectrum protection against influenza viruses. Here, we show that OVX836 intramuscular (IM) immunization induces higher numbers of NP-specific IFNγ-producing CD8+ T-cells in the lung, compared to mutant NP (NPm) and wild-type NP (NPwt), which form monomeric and trimeric structures, respectively. OVX836 induces cytotoxic CD8+ T-cells and high frequencies of lung TRM CD8+ T-cells, while inducing solid protection against lethal influenza virus challenges for at least 90 days. Adoptive transfer experiments demonstrated that protection against diverse influenza subtypes is mediated by NP-specific CD8+ T-cells isolated from the lung and spleen following OVX836 vaccination. OVX836 induces a high number of NP-specific lung CD8+ TRM-cells for long-term protection against influenza viruses.

scholarly journals Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

2013 ◽  
Vol 121 (10) ◽  
pp. 1187-1193 ◽  
Author(s):  
Kathryn A. Ramsey ◽  
Rachel E. Foong ◽  
Peter D. Sly ◽  
Alexander N. Larcombe ◽  
Graeme R. Zosky
Keyword(s):  
Early Life ◽  
Influenza A ◽  
Arsenic Exposure

scholarly journals The Circadian-clock Regulates the Arabidopsis Gravitropic Response

2021 ◽  
Vol 9 (1) ◽  
pp. 170-185
Author(s):  
Joseph S. Tolsma ◽  
Kaetlyn T. Ryan ◽  
Jacob J. Torres ◽  
Jeffrey T. Richards ◽  
Zach Richardson ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Simulated Microgravity ◽  
Primary Root ◽  
Time Of Day ◽  
Plant Roots ◽  
Gravity Vector ◽  
Gravitropic Response ◽  
2D Clinostat ◽  
Initial Change

Abstract For long-term space missions, it is necessary to understand how organisms respond to changes in gravity. Plant roots are positively gravitropic; the primary root grows parallel to gravity's pull even after being turned away from the direction of gravity. We examined if this gravitropic response varies depending on the time of day reorientation occurs. When plants were reoriented in relation to the gravity vector or placed in simulated microgravity, the magnitude of the root gravitropic response varied depending on the time of day the initial change in gravity occurred. The response was greatest when plants were reoriented at dusk, just before a period of rapid growth, and were minimal just before dawn as the plants entered a period of reduced root growth. We found that this variation in the magnitude of the gravitropic response persisted in constant light (CL) suggesting the variation is circadian-regulated. Gravitropic responses were disrupted in plants with disrupted circadian clocks, including plants overexpressing Circadian-clock Associated 1 (CCA1) and elf3-2, in the reorientation assay and on a 2D clinostat. These findings indicate that circadian-regulated pathways modulate the gravitropic responses, thus, highlighting the importance of considering and recording the time of day gravitropic experiments are performed.

scholarly journals The circadian clock contributes to the long-term water use efficiency of Arabidopsis

2019 ◽  
Author(s):  
Noriane M. L. Simon ◽  
Calum A. Graham ◽  
Nicholas E. Comben ◽  
Alistair M. Hetherington ◽  
Antony N. Dodd
Keyword(s):  
Circadian Clock ◽  
Water Use Efficiency ◽  
Water Use ◽  
Biomass Accumulation ◽  
Time Of Day ◽  
Circadian Oscillator ◽  
Circadian Regulation ◽  
Use Efficiency ◽  
The Impact

AbstractIn plants, water use efficiency is a complex trait derived from numerous physiological and developmental characteristics. Here, we investigated the involvement of circadian regulation in long-term water use efficiency. Circadian rhythms are generated by the circadian oscillator, which provides a cellular measure of the time of day. In plants, the circadian oscillator contributes to the regulation of many aspects of physiology, including stomatal opening, the rate of photosynthesis, carbohydrate metabolism and developmental processes. We investigated in Arabidopsis the impact of the misregulation of genes encoding a large number of components of the circadian oscillator upon whole plant, long-term water use efficiency. From this, we identified a role for the circadian oscillator in water use efficiency. This appears to be due to contributions of the circadian clock to the control of transpiration and biomass accumulation. We also identified that the circadian oscillator within guard cells can contribute to long-term water use efficiency. Our experiments indicate that knowledge of circadian regulation will be important for developing future crops that use water more efficiently.One-sentence summaryThe circadian clock in Arabidopsis makes an important contribution to long-term water use efficiency.

scholarly journals High Rate of Chronic Villitis in Placentas of Pregnancies Complicated by Influenza A/H1N1 Infection

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Wouter J. Meijer ◽  
Annemarie M. J. Wensing ◽  
Hein W. Bruinse ◽  
Peter G. J. Nikkels
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Negative Impact ◽  
Influenza Infection ◽  
Placental Tissue ◽  
High Rate ◽  
H1n1 Infection ◽  
Influenza A H1n1 ◽  
Polymerase Chain ◽  
Chronic Villitis

Introduction. Pandemic influenza A/H1N1 infection during pregnancy has a negative impact on several aspects of pregnancy outcome. As yet, no elucidating mechanism has been revealed for these effects. We investigated whether placentas of pregnancies complicated by 2009 influenza A/H1N1 infection demonstrated an increased rate of chronic villitis and whether this villitis was caused by influenza virus.Methods. We performed a cohort study on 145 pregnant outpatients during the 2009-2010 influenza A H1N1 pandemic. The placentas of patients with influenza infection were examined for histologic signs of chronic villitis. In case of villitis, polymerase chain reaction (PCR) on influenza virus was performed on placental tissue.Results. 29 patients had influenza infection. Placentas of 15 of these patients were collected and examined. In 7 cases (47%) chronic villitis was detected. Placental weight and birth weight of the neonates did not differ between cases with and without chronic villitis. In all cases PCR was negative for influenza.Conclusion. In our series, chronic villitis was present in a high proportion of placentas of pregnancies complicated by 2009 influenza A/H1N1 infection. We could not demonstrate the presence of influenza virus in placental tissue.

scholarly journals Infection of mice with influenza A/WSN/33 (H1N1) virus alters alveolar type II cell phenotype

2015 ◽  
Vol 308 (7) ◽  
pp. L628-L638 ◽  
Author(s):  
Christian C. Hofer ◽  
Parker S. Woods ◽  
Ian C. Davis
Keyword(s):  
Influenza A ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
Normal Lung ◽  
Cell Phenotype ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii ◽  
Atii Cell ◽  
The Impact

Influenza viruses cause acute respiratory disease of great importance to public health. Alveolar type II (ATII) respiratory epithelial cells are central to normal lung function and are a site of influenza A virus replication in the distal lung. However, the consequences of infection for ATII cell function are poorly understood. To determine the impact of influenza infection on ATII cells we used C57BL/6-congenic SP-CGFP mice that express green fluorescent protein (GFP) under the control of the surfactant protein-C (SP-C) promoter, which is only active in ATII cells. Most cells isolated from the lungs of uninfected SP-CGFP mice were GFP+ but did not express the alveolar type I (ATI) antigen podoplanin (PODO). ATII cells were also EpCAM+ and α2,3-linked sialosaccharide+. Infection with influenza A/WSN/33 virus caused severe hypoxemia and pulmonary edema. This was accompanied by loss of whole lung GFP fluorescence, reduced ATII cell yields, increased ATII cell apoptosis, reduced SP-C gene and protein expression in ATII cell lysates, and increased PODO gene and protein levels. Flow cytometry indicated that infection decreased GFP+/PODO− cells and increased GFP−/PODO+ and GFP−/PODO− cells. Very few GFP+/PODO+ cells were detectable. Finally, infection resulted in a significant decline in EpCAM expression by PODO+ cells, but had limited effects on α2,3-linked sialosaccharides. Our findings indicate that influenza infection results in a progressive differentiation of ATII cells into ATI-like cells, possibly via an SP-C−/PODO− intermediate, to replace dying or dead ATI cells. However, impaired SP-C synthesis is likely to contribute significantly to reduced lung compliance in infected mice.

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