Figure 1. Neonatal and elderly mice have increased mortality compared to young adult mice with impaired control of bacteria at the site of infection and decreased activation of leukocytes.

A. Neonatal and elderly mice had increased mortality after CS sepsis compared to young adult mice with the same insult (P<0.05) over 7 days. Neonate (n=22), Young Adult (n=20), Elderly (n=21). B. One day after sepsis both neonatal and elderly mice had significantly increased bacterial counts in the blood (* p<0.0001, One-way ANOVA), and in the peritoneum †p=0.019, One-way ANOVA); with elderly mice having the most severe impairments in clearing bacteria (Blood-p<0.001, Peritoneal wash-p<0.05; Tukey’s Multiple Comparisons post-hoc test) (n=3–4, results shown are from two or more independent experiments). C. Functional pathway analysis showed that elderly mice had down-regulation of genes involved in the the activation of luekocytes, whereas young adult mice had significant upregulation of these same genes (Supplemental Table 1). Neonatal mice niether up or down regulated a large enough number of genes involved in leukocyte activation at a significance level of p<0.001. Heatmaps show the of gene expression of the functional category “Immune Cell Trafficking-Activation” one day after sepsis in neonatal, young adult, and elderly mice. Orange represents pathways with an over-expression of genes leading to the activation of the pathway, whereas blue represents pathways with an over-expression of genes whose activation will lead to down-regulation of the pathway. White represents genes that are neither up or down regulated to significance level of p<0.001. Graph shows the various subcategories and their corresponding significance level (Z-score) of up or down regulation. From left to right, categories include “activation of leukocytes,” “activation of mononuclear leukocytes,” “activation of granulocytes,” and “activation of neutrophils.” (* Z-score >2). See Supplemental Table 2 for a complete list of genes in presented pathways.