Chronic morphine and HIV-1 Tat, in the context of systemic S. pneumoniae co-infection, differentially modulated induction of TLR2/4, which consequently facilitated trafficking of TLR2 → CD3 + CCR5+ and TLR4 → Ly6C+(CCR5+/CXCR4+) immune cells into the CNS. This evidence concerns the gene TLR4 and coinfection.