The top downregulated pathways in both the blood and the spleen involved lymphocyte signaling pathways and T lymphocyte apoptosis pathways (Fig 1A and 1B) that included lower abundance of several genes following L. monocytogenes infection such as Cd4, Cd28, Icos, Nfatc1, Nfatc2 and Trat1. Such changes in gene expression were validated by RT-PCR for the genes Icos and Nfatc1 (Fig 1C) and also validated by microarray analysis of blood and spleen from an independent infection experiment (data not shown). Here, ICOS is linked to infection.