Here, we provide the first evidence showing that BDNF deletion resulted in a strong increase in the S. pneumoniae-induced phosphorylation of NF-κB p65 and phosphorylation of p38 MAPK through TLR2/MyD88 and NOD2 downstream signaling, lead to the excessive secretion of pro-inflammatory cytokines, thereby exacerbating brain inflammation and further injury (Figure 10). The gene discussed is TLR2; the disease is inflammatory response.