In E. coli challenged chicks: ↓ reduced clinical scores in CpG-ODN treated chicks  ↑ Upregulation of proinflammatory cytokines [IL-1, IL-4, IL-6, IL-10, IL-18, IFN-γ, IFN-α, and lipopolysaccharide induced tumor necrosis factor (LITAF)] in spleen and lungs  ↑ Significant enrichment of macrophages, CD4+ and CD8+ T-cell subsets in both spleen and lungs  ↑ Upregulation of CD40 but not CD86  ↑ CD4 and CD8 expression  ↑ Protection in neonatal chicks against E. coli infection. The gene discussed is CD40; the disease is escherichia coli infection.