Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection

Greg I. Lee, Jordy Saravia, Dahui You, Bishwas Shrestha, Sridhar Jaligama, Valerie Y. Hebert, Tammy R. Dugas, Stephania Cormier

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Exposures to elevated levels of particulate matter (PM) enhance severity of influenza virus infection in infants. The biological mechanism responsible for this phenomenon is unknown. The recent identification of environmentally persistent free radicals (EPFRs) associated with PM from a variety of combustion sources suggests its role in the enhancement of influenza disease severity. Methods: Neonatal mice (< seven days of age) were exposed to DCB230 (combustion derived PM with a chemisorbed EPFR), DCB50 (non-EPFR PM sample), or air for 30 minutes/day for seven consecutive days. Four days post-exposure, neonates were infected with influenza intranasally at 1.25 TCID50/neonate. Neonates were assessed for morbidity (% weight gain, peak pulmonary viral load, and viral clearance) and percent survival. Lungs were isolated and assessed for oxidative stress (8-isoprostanes and glutathione levels), adaptive immune response to influenza, and regulatory T cells (Tregs). The role of the EPFR was also assessed by use of transgenic mice expressing human superoxide dismutase 2. Results: Neonates exposed to EPFRs had significantly enhanced morbidity and decreased survival following influenza infection. Increased oxidative stress was also observed in EPFR exposed neonates. This correlated with increased pulmonary Tregs and dampened protective T cell responses to influenza infection. Reduction of EPFR-induced oxidative stress attenuated these effects. Conclusions: Neonatal exposure to EPFR containing PM resulted in pulmonary oxidative stress and enhanced influenza disease severity. EPFR-induced oxidative stress resulted in increased presence of Tregs in the lungs and subsequent suppression of adaptive immune response to influenza.

Original languageEnglish (US)
Article number57
JournalParticle and Fibre Toxicology
Volume11
Issue number1
DOIs
StatePublished - Oct 30 2014

Fingerprint

Virus Diseases
Orthomyxoviridae
Viruses
Free Radicals
Human Influenza
Oxidative stress
Particulate Matter
Oxidative Stress
Newborn Infant
Lung
8-epi-prostaglandin F2alpha
T-cells
Adaptive Immunity
Morbidity
Survival
Regulatory T-Lymphocytes
Infection
Viral Load
Transgenic Mice
Weight Gain

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection. / Lee, Greg I.; Saravia, Jordy; You, Dahui; Shrestha, Bishwas; Jaligama, Sridhar; Hebert, Valerie Y.; Dugas, Tammy R.; Cormier, Stephania.

In: Particle and Fibre Toxicology, Vol. 11, No. 1, 57, 30.10.2014.

Research output: Contribution to journalArticle

Lee, Greg I. ; Saravia, Jordy ; You, Dahui ; Shrestha, Bishwas ; Jaligama, Sridhar ; Hebert, Valerie Y. ; Dugas, Tammy R. ; Cormier, Stephania. / Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection. In: Particle and Fibre Toxicology. 2014 ; Vol. 11, No. 1.
@article{f5f07f6212da4c8eb6b7bc3872392ef2,
title = "Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection",
abstract = "Background: Exposures to elevated levels of particulate matter (PM) enhance severity of influenza virus infection in infants. The biological mechanism responsible for this phenomenon is unknown. The recent identification of environmentally persistent free radicals (EPFRs) associated with PM from a variety of combustion sources suggests its role in the enhancement of influenza disease severity. Methods: Neonatal mice (< seven days of age) were exposed to DCB230 (combustion derived PM with a chemisorbed EPFR), DCB50 (non-EPFR PM sample), or air for 30 minutes/day for seven consecutive days. Four days post-exposure, neonates were infected with influenza intranasally at 1.25 TCID50/neonate. Neonates were assessed for morbidity ({\%} weight gain, peak pulmonary viral load, and viral clearance) and percent survival. Lungs were isolated and assessed for oxidative stress (8-isoprostanes and glutathione levels), adaptive immune response to influenza, and regulatory T cells (Tregs). The role of the EPFR was also assessed by use of transgenic mice expressing human superoxide dismutase 2. Results: Neonates exposed to EPFRs had significantly enhanced morbidity and decreased survival following influenza infection. Increased oxidative stress was also observed in EPFR exposed neonates. This correlated with increased pulmonary Tregs and dampened protective T cell responses to influenza infection. Reduction of EPFR-induced oxidative stress attenuated these effects. Conclusions: Neonatal exposure to EPFR containing PM resulted in pulmonary oxidative stress and enhanced influenza disease severity. EPFR-induced oxidative stress resulted in increased presence of Tregs in the lungs and subsequent suppression of adaptive immune response to influenza.",
author = "Lee, {Greg I.} and Jordy Saravia and Dahui You and Bishwas Shrestha and Sridhar Jaligama and Hebert, {Valerie Y.} and Dugas, {Tammy R.} and Stephania Cormier",
year = "2014",
month = "10",
day = "30",
doi = "10.1186/s12989-014-0057-1",
language = "English (US)",
volume = "11",
journal = "Particle and Fibre Toxicology",
issn = "1743-8977",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection

AU - Lee, Greg I.

AU - Saravia, Jordy

AU - You, Dahui

AU - Shrestha, Bishwas

AU - Jaligama, Sridhar

AU - Hebert, Valerie Y.

AU - Dugas, Tammy R.

AU - Cormier, Stephania

PY - 2014/10/30

Y1 - 2014/10/30

N2 - Background: Exposures to elevated levels of particulate matter (PM) enhance severity of influenza virus infection in infants. The biological mechanism responsible for this phenomenon is unknown. The recent identification of environmentally persistent free radicals (EPFRs) associated with PM from a variety of combustion sources suggests its role in the enhancement of influenza disease severity. Methods: Neonatal mice (< seven days of age) were exposed to DCB230 (combustion derived PM with a chemisorbed EPFR), DCB50 (non-EPFR PM sample), or air for 30 minutes/day for seven consecutive days. Four days post-exposure, neonates were infected with influenza intranasally at 1.25 TCID50/neonate. Neonates were assessed for morbidity (% weight gain, peak pulmonary viral load, and viral clearance) and percent survival. Lungs were isolated and assessed for oxidative stress (8-isoprostanes and glutathione levels), adaptive immune response to influenza, and regulatory T cells (Tregs). The role of the EPFR was also assessed by use of transgenic mice expressing human superoxide dismutase 2. Results: Neonates exposed to EPFRs had significantly enhanced morbidity and decreased survival following influenza infection. Increased oxidative stress was also observed in EPFR exposed neonates. This correlated with increased pulmonary Tregs and dampened protective T cell responses to influenza infection. Reduction of EPFR-induced oxidative stress attenuated these effects. Conclusions: Neonatal exposure to EPFR containing PM resulted in pulmonary oxidative stress and enhanced influenza disease severity. EPFR-induced oxidative stress resulted in increased presence of Tregs in the lungs and subsequent suppression of adaptive immune response to influenza.

AB - Background: Exposures to elevated levels of particulate matter (PM) enhance severity of influenza virus infection in infants. The biological mechanism responsible for this phenomenon is unknown. The recent identification of environmentally persistent free radicals (EPFRs) associated with PM from a variety of combustion sources suggests its role in the enhancement of influenza disease severity. Methods: Neonatal mice (< seven days of age) were exposed to DCB230 (combustion derived PM with a chemisorbed EPFR), DCB50 (non-EPFR PM sample), or air for 30 minutes/day for seven consecutive days. Four days post-exposure, neonates were infected with influenza intranasally at 1.25 TCID50/neonate. Neonates were assessed for morbidity (% weight gain, peak pulmonary viral load, and viral clearance) and percent survival. Lungs were isolated and assessed for oxidative stress (8-isoprostanes and glutathione levels), adaptive immune response to influenza, and regulatory T cells (Tregs). The role of the EPFR was also assessed by use of transgenic mice expressing human superoxide dismutase 2. Results: Neonates exposed to EPFRs had significantly enhanced morbidity and decreased survival following influenza infection. Increased oxidative stress was also observed in EPFR exposed neonates. This correlated with increased pulmonary Tregs and dampened protective T cell responses to influenza infection. Reduction of EPFR-induced oxidative stress attenuated these effects. Conclusions: Neonatal exposure to EPFR containing PM resulted in pulmonary oxidative stress and enhanced influenza disease severity. EPFR-induced oxidative stress resulted in increased presence of Tregs in the lungs and subsequent suppression of adaptive immune response to influenza.

UR - http://www.scopus.com/inward/record.url?scp=84920857732&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84920857732&partnerID=8YFLogxK

U2 - 10.1186/s12989-014-0057-1

DO - 10.1186/s12989-014-0057-1

M3 - Article

VL - 11

JO - Particle and Fibre Toxicology

JF - Particle and Fibre Toxicology

SN - 1743-8977

IS - 1

M1 - 57

ER -