In the current study, we explored the contribution of specific chemokine receptors, i.e., CXCR4 and CCR5, in differential leukocyte trafficking into the CNS of mice following chronic morphine, HIV-1 Transactivator of transcription (Tat) protein, and/or co-infection with Streptococcus pneumoniae. Here, CXCR4 is linked to coinfection.