Influenza virus induces variable weight loss and inflammation in outbred mice.

<p>Diversity outbred mice were infected with 1x10⁶ pfu of influenza A/California/07/2009 virus and were harvested five days later. A, weight loss over time as percentage of pre-challenge starting weight (N=30). B, correlation between starting weight and weight loss percentage (N=30). C, bronchoalveolar lavage cell counts correlated with weight loss percentage (N=14). D, bronchoalveolar lavage protein concentration correlated with weight loss percentage (N=14). R, Pearson’s Rho; P indicates significance as listed. Solid bar indicates group mean.</p

Inflammatory cytokine levels correlated with weight loss or viral burden in influenza virus, <i>S. aureus</i> co-infected mice.

<p>Diversity outbred mice were infected with 1x10⁶ pfu of influenza A/California/07/2009 virus followed by infection with <i>S. aureus</i> USA300 on day 6 and then harvested 2 days later. A, weight loss percentage correlated with cytokine expression in lung homogenate (by Lincoplex) (N=12). B-D, influenza virus M protein gene expression correlated with cytokine expression in lung homogenate (N=12). E, F variable pathology in co-infected individual mice. R, Pearson’s Rho; P indicates significance as listed.</p

Inflammatory cytokine levels correlated with influenza viral burden or weight loss.

<p>Diversity outbred mice were infected with 1x10⁶ pfu of influenza A/California/07/2009 virus and were harvested five days later. A, cytokine levels in lung homogenate (by Lincoplex) correlated with influenza virus M protein gene expression (by qRT-PCR) (N=13). B, cytokine levels in serum correlated with influenza virus M protein gene expression (N=14). C, D, cytokine levels in serum correlated with weight loss percentage (N=14). R, Pearson’s Rho; P indicates significance as listed.</p

Viral burden correlates with weight loss in outbred mice.

<p>Diversity outbred mice were infected with 1x10⁶ pfu of influenza A/California/07/2009 virus and were harvested five or eight days later. A, day five influenza virus M protein gene expression (determined by qRT-PCR) correlated with weight loss percentage (N=13). B, day eight influenza virus M protein gene expression correlated with weight loss percentage (N=13). R, Pearson’s Rho; P indicates significance as listed.</p

Influenza virus, <i>S. aureus</i> co-infection results in variable bacterial burden in outbred mice.

<p>Diversity outbred mice were infected with 1x10⁶ pfu of influenza A/California/07/2009 virus or vehicle control followed by infection with <i>S. aureus</i> USA300 on day 6 and then harvested 2 days later. A, weight loss induced by <i>S. aureus</i> infection alone in outbred mice (N=15). B, weight loss induced by <i>S. aureus</i> alone correlated with bacterial burden in lung homogenate (N=15). C, bacterial burden in the lungs of <i>S. aureus</i> only and co-infected mice (N=15, 12). D, weight loss induced by <i>S. aureus</i>, influenza virus co-infection correlated with bacterial burden in lung homogenate (N=12). R, Pearson’s Rho; P indicates significance as listed. Solid bar indicates group mean.</p

Inflammatory cytokine levels correlated with influenza virus induced weight loss at day eight.

<p>Diversity outbred mice were infected with 1x10⁶ pfu of influenza A/California/07/2009 virus and were harvested eight days later. A-C, weight loss percentage correlated with lung homogenate cytokine concentration (by Lincoplex) (N=12). R, Pearson’s Rho; P indicates significance as listed.</p

Cytokine gene expression correlated with influenza viral burden or weight loss.

<p>Diversity outbred mice were infected with 1x10⁶ pfu of influenza A/California/07/2009 virus and were harvested five days later. A, C, E, F, influenza virus M protein gene expression correlated with cytokine expression (by qRT-PCR) (N=13). B, D, weight loss percentage correlated with cytokine expression (N=13). R, Pearson’s Rho; P indicates significance as listed.</p

<i>S. aureus</i> infection results in variable lung pathology in outbred mice.

<p>Diversity outbred mice were infected <i>S. aureus</i> USA300 and then harvested 2 days later. A-D, lung pathology from individual mice with weight loss percentage (upper number) and <i>S. aureus</i> burden (lower number, x10³ cfu/ml). </p

Variable lung pathology in influenza virus infected outbred mice.

<p>Diversity outbred mice were infected with 1x10⁶ pfu of influenza A/California/07/2009 virus and were harvested five days later. A, B, individual mice with similar influenza viral burden (relative M protein gene expression, lower number) but disparate weight loss (weight loss percentage, upper number). C, D, individual mice with similar weight loss but different viral burdens. E, individual mouse with extreme weight loss and high viral burden, but with minimal lung inflammation pathology. F, individual mouse with no weight loss and low viral burden, but with significant lung injury. G, histologic scoring of lung parenchymal inflammation. </p

Inflammatory cytokine levels correlated with weight loss or bacterial burden in <i>S. aureus</i> infected mice.

<p>Diversity outbred mice were infected <i>S. aureus</i> USA300 and then harvested 2 days later. A, C, E, F, weight loss percentage correlated with cytokine expression in lung homogenate (by Lincoplex) (N=15). B, D, bacterial burden correlated with cytokine expression in lung homogenate (N=15). R, Pearson’s Rho; P indicates significance as listed.</p