A Neonatal murine model of mrsa pneumonia

Elizabeth Fitzpatrick, Dahui You, Bishwas Shrestha, David Siefker, Vivek Patel, Nikki Yadav, Sridhar Jaligama, Stephania Cormier

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Abstract

Pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of morbidity and mortality in infants particularly following lower respiratory tract viral infections such as Respiratory Syncytial Virus (RSV). However, the mechanisms by which co-infection of infants by MRSA and RSV cause increased lung pathology are unknown. Because the infant immune system is qualitatively and quantitatively different from adults we developed a model of infant MRSA pneumonia which will allow us to investigate the effects of RSV co-infection on disease severity. We infected neonatal and adult mice with increasing doses of MRSA and demonstrate that neonatal mice have delayed kinetics in clearing the bacteria in comparison to adult mice. There were differences in recruitment of immune cells into the lung following infection. Adult mice exhibited an increase in neutrophil recruitment that coincided with reduced bacterial titers followed by an increase in macrophages. Neonatal mice, however, exhibited an early increase in neutrophils that did not persist despite continued presence of the bacteria. Unlike the adult mice, neonatal mice failed to exhibit an increase in macrophages. Neonates exhibited a decrease in phagocytosis of MRSA suggesting that the decrease in clearance was partially due to deficient phagocytosis of the bacteria. Both neonates and adults responded with an increase in pro-inflammatory cytokines following infection. However, in contrast to the adult mice, neonates did not express constitutive levels of the anti-microbial peptide Reg3γ in the lung. Infection of neonates did not stimulate expression of the co-stimulatory molecule CD86 by dendritic cells and neonates exhibited a diminished T cell response compared to adult mice. Overall, we have developed a neonatal model of MRSA pneumonia that displays a similar delay in bacterial clearance as is observed in the neonatal intensive care unit and will be useful for performing co-infection studies.

Original languageEnglish (US)
Article numbere0169273
JournalPLoS ONE
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2017

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Methicillin
pneumonia
Pneumonia
neonates
animal models
Methicillin-Resistant Staphylococcus aureus
Viruses
Bacteria
Newborn Infant
Macrophages
mixed infection
mice
Coinfection
Staphylococcal Pneumonia
lungs
Respiratory Syncytial Viruses
phagocytosis
infection
viruses
Phagocytosis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Fitzpatrick, E., You, D., Shrestha, B., Siefker, D., Patel, V., Yadav, N., ... Cormier, S. (2017). A Neonatal murine model of mrsa pneumonia. PLoS ONE, 12(1), [e0169273]. https://doi.org/10.1371/journal.pone.0169273

A Neonatal murine model of mrsa pneumonia. / Fitzpatrick, Elizabeth; You, Dahui; Shrestha, Bishwas; Siefker, David; Patel, Vivek; Yadav, Nikki; Jaligama, Sridhar; Cormier, Stephania.

In: PLoS ONE, Vol. 12, No. 1, e0169273, 01.01.2017.

Research output: Contribution to journalArticle

Fitzpatrick, E, You, D, Shrestha, B, Siefker, D, Patel, V, Yadav, N, Jaligama, S & Cormier, S 2017, 'A Neonatal murine model of mrsa pneumonia', PLoS ONE, vol. 12, no. 1, e0169273. https://doi.org/10.1371/journal.pone.0169273
Fitzpatrick E, You D, Shrestha B, Siefker D, Patel V, Yadav N et al. A Neonatal murine model of mrsa pneumonia. PLoS ONE. 2017 Jan 1;12(1). e0169273. https://doi.org/10.1371/journal.pone.0169273
Fitzpatrick, Elizabeth ; You, Dahui ; Shrestha, Bishwas ; Siefker, David ; Patel, Vivek ; Yadav, Nikki ; Jaligama, Sridhar ; Cormier, Stephania. / A Neonatal murine model of mrsa pneumonia. In: PLoS ONE. 2017 ; Vol. 12, No. 1.
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