scholarly journals Neonatal hyperoxia alters the host response to influenza A virus infection in adult mice through multiple pathways

2013 ◽  
Vol 305 (4) ◽  
pp. L282-L290 ◽  
Author(s):  
Bradley W. Buczynski ◽  
Min Yee ◽  
Kyle C. Martin ◽  
B. Paige Lawrence ◽  
Michael A. O'Reilly
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Lung Development ◽  
Host Response ◽  
Influenza A ◽  
Leukocyte Recruitment ◽  
Newborn Mice ◽  
Adult Mice ◽  
Influenza A Virus Infection ◽  
Neonatal Hyperoxia

Exposing preterm infants or newborn mice to high concentrations of oxygen disrupts lung development and alters the response to respiratory viral infections later in life. Superoxide dismutase (SOD) has been separately shown to mitigate hyperoxia-mediated changes in lung development and attenuate virus-mediated lung inflammation. However, its potential to protect adult mice exposed to hyperoxia as neonates against viral infection is not known. Here, transgenic mice overexpressing extracellular (EC)-SOD in alveolar type II epithelial cells are used to test whether SOD can alleviate the deviant pulmonary response to influenza virus infection in adult mice exposed to hyperoxia as neonates. Fibrotic lung disease, observed following infection in wild-type (WT) mice exposed to hyperoxia as neonates, was prevented by overexpression of EC-SOD. However, leukocyte recruitment remained excessive, and levels of monocyte chemoattractant protein (MCP)-1 remained modestly elevated following infection in EC-SOD Tg mice exposed to hyperoxia as neonates. Because MCP-1 is often associated with pulmonary inflammation and fibrosis, the host response to infection was concurrently evaluated in adult Mcp-1 WT and Mcp-1 knockout mice exposed to neonatal hyperoxia. In contrast to EC-SOD, excessive leukocyte recruitment, but not lung fibrosis, was dependent upon MCP-1. Our findings demonstrate that neonatal hyperoxia alters the inflammatory and fibrotic responses to influenza A virus infection through different pathways. Therefore, these data suggest that multiple therapeutic strategies may be needed to provide complete protection against diseases attributed to prematurity and early life exposure to oxygen.

scholarly journals Phosphoproteomics to Characterize Host Response During Influenza A Virus Infection of Human Macrophages

2016 ◽  
Vol 15 (10) ◽  
pp. 3203-3219 ◽  
Author(s):  
Sandra Söderholm ◽  
Denis E. Kainov ◽  
Tiina Öhman ◽  
Oxana V. Denisova ◽  
Bert Schepens ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Host Response ◽  
Influenza A ◽  
Human Macrophages ◽  
Influenza A Virus Infection

scholarly journals Oxygen-dependent changes in lung development do not affect epithelial infection with influenza A virus

2017 ◽  
Vol 313 (5) ◽  
pp. L940-L949 ◽  
Author(s):  
William Domm ◽  
Min Yee ◽  
Ravi S. Misra ◽  
Robert Gelein ◽  
Aitor Nogales ◽  
...  
Keyword(s):  
Hong Kong ◽  
Influenza A Virus ◽  
Lung Development ◽  
Influenza A ◽  
Supplemental Oxygen ◽  
Modest Increase ◽  
Alveolar Epithelial ◽  
Adult Mice ◽  
Persistent Inflammation ◽  
Neonatal Hyperoxia

Infants born prematurely often require supplemental oxygen, which contributes to aberrant lung development and increased pulmonary morbidity following a respiratory viral infection. We have been using a mouse model to understand how early-life hyperoxia affects the adult lung response to influenza A virus (IAV) infection. Prior studies showed how neonatal hyperoxia (100% oxygen) increased sensitivity of adult mice to infection with IAV [IAV (A/Hong Kong/X31) H3N2] as defined by persistent inflammation, pulmonary fibrosis, and mortality. Since neonatal hyperoxia alters lung structure, we used a novel fluorescence-expressing reporter strain of H1N1 IAV [A/Puerto Rico/8/34 mCherry (PR8-mCherry)] to evaluate whether it also altered early infection of the respiratory epithelium. Like Hong Kong/X31, neonatal hyperoxia increased morbidity and mortality of adult mice infected with PR8-mCherry. Whole lung imaging and histology suggested a modest increase in mCherry expression in adult mice exposed to neonatal hyperoxia compared with room air-exposed animals. However, this did not reflect an increase in airway or alveolar epithelial infection when mCherry-positive cells were identified and quantified by flow cytometry. Instead, a modest increase in the number of CD45-positive macrophages expressing mCherry was detected. While neonatal hyperoxia does not alter early epithelial infection with IAV, it may increase the activity of macrophages toward infected cells, thereby enhancing early epithelial injury.

Vitamin A Deficiency Impairs Some Aspects of the Host Response to Influenza A Virus Infection in BALB/c Mice

1993 ◽  
Vol 123 (5) ◽  
pp. 823-833 ◽  
Author(s):  
Charles B. Stephensen ◽  
Sharon R. Blount ◽  
Trenton R. Schoeb ◽  
Jong Y. Park
Keyword(s):  
Virus Infection ◽  
Vitamin A ◽  
Influenza A Virus ◽  
Host Response ◽  
Influenza A ◽  
Vitamin A Deficiency ◽  
Influenza A Virus Infection

scholarly journals Neonatal Oxygen Increases Sensitivity to Influenza A Virus Infection in Adult Mice by Suppressing Epithelial Expression of Ear1

2012 ◽  
Vol 181 (2) ◽  
pp. 441-451 ◽  
Author(s):  
Michael A. O'Reilly ◽  
Min Yee ◽  
Bradley W. Buczynski ◽  
Peter F. Vitiello ◽  
Peter C. Keng ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Adult Mice ◽  
Influenza A Virus Infection

scholarly journals Neonatal hyperoxia leads to persistent alterations in NK responses to influenza A virus infection

2015 ◽  
Vol 308 (1) ◽  
pp. L76-L85 ◽  
Author(s):  
Emma C. Reilly ◽  
Kyle C. Martin ◽  
Guang-bi Jin ◽  
Min Yee ◽  
Michael A. O'Reilly ◽  
...  
Keyword(s):  
Nk Cells ◽  
Influenza A Virus ◽  
Lung Development ◽  
Influenza A ◽  
Nk Cell ◽  
Normal Lung ◽  
Low Birth Weight Infants ◽  
Newborn Mice ◽  
Peripheral Tissues ◽  
Neonatal Hyperoxia

Respiratory distress in preterm or low birth weight infants is often treated with supplemental oxygen. However, this therapy can disrupt normal lung development and architecture and alter responses to respiratory insults. Similarly, exposure of newborn mice to 100% oxygen during saccular lung development leads to permanent alveolar simplification, and upon challenge with influenza A virus, mice exhibit reduced host resistance. Natural killer (NK) cells are key players in antiviral immunity, and emerging evidence suggest they also help to maintain homeostasis in peripheral tissues, including the lung, by promoting epithelial cell regeneration via IL-22. We tested the hypothesis that adult mice exposed to hyperoxia as neonates have modified NK cell responses to infection. We report here that mice exposed to neonatal hyperoxia had fewer IL-22+ NK cells in their lungs after influenza virus challenge and a parallel increase in IFN-γ+ NK cells. Using reciprocal bone marrow chimeric mice, we show that exposure of either hematopoietic or nonhematopoietic cells was sufficient to increase the severity of infection and to diminish the frequency of IL-22+ NK cells in the infected lung. Overall, our findings suggest that neonatal hyperoxia leads to long-term changes in the reparative vs. cytotoxic nature of NK cells and that this is due in part to intrinsic changes in hematopoietic cells. These differences may contribute to how oxygen alters the host response to respiratory viral infections.

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