<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

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

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 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 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

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

Effect of IL-22 (CC10-IL-22) on cytokine and chemokine production in OVA-induced allergic asthma.

<p>Th1 cytokine, IFN-γ, and Th2 cytokines, IL-4 and IL-13, Th17 cytokine IL-17A, and chemokine eotaxin in the BAL were measured by ELISA. The number of animals in each group was indicated and data were shown as Mean±SEM. **<i>P</i><0.01 (unpaired Student t-test).</p

IL-22 alleviated OVA-induced eosinophilic inflammation in the lung.

<p>(A) High levels of IL-22 cytokine were seen in the BAL of PBS and OVA-stimulated IL-22 Tg(+) mice without difference between the two groups (<i>P</i>>0.05). When compared to Tg(−) mice, IL-22 concentrations in the BAL of Tg(+) mice were much higher than that in PBS and OVA-stimulated control groups (<i>P</i><0.0001). (B, C) BAL total cell and differentials counts showed that OVA-stimulated IL-22 Tg(+) group had a much higher percentage of eosinophils compared to OVA-stimulated Tg(−) mice (<i>P</i><0.0001), but there is no difference in the total cell counts (<i>P</i>>0.05). (D) Lung histology of OVA-induced allergic asthma in SPC-IL-22 Tg(+) mice and Tg(−) mice, H&E, IHC for MBP, and Alcian blue staining showed that OVA-induced IL-22 Tg(−) group had much more severe airway inflammation compared to OVA-induced IL-22 Tg(+) group.</p

Effect of IL-22 (SPC-IL-22) on OVA-induced systemic and local immune responses.

<p>Splenocytes and lymphocytes from peribronchial draining lymph nodes (DLN) from IL-22 Tg(+) and Tg(−) mice after OVA challenge were cultured and stimulated with medium control, OVA or CD3/CD28. Th1 cytokine, IFN-γ, and Th2 cytokine, IL-13 in the supernatant were measured by ELISA. The number of animals used in the experiments was indicated and data were shown as Mean±SEM. *<i>P</i><0.05 and **<i>P</i><0.01 (unpaired Student t-test).</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