Is decreased HIV-1 infectivity of placental macrophages caused by high levels of beta-chemokines?

The objective of this study was to determine the effect of beta-chemokine secretion on HIV infection of placental macrophages (HF) as compared to monocyte-derived macrophages (MDM). For this purpose, we measured chemokine production in supematants of LPS stimulated and unstimulated HF and MDM. LPS stimulated cultures produced 3 to 10 times higher levels of MIP-1alpha, MIP-1beta and RANTES than unstimulated cultures. The level of MIP-1beta was the highest of the three chemokines secreted upon stimulation of HF cells. Cell cultures were inoculated with HIV-BaL, a R5 virus, and tested for p24 antigen and chemokine production at days 5 and 10 post-infection (P.I.). We did not find significant differences in the level of chemokines produced by HIV-1-infected and uninfected MDM and HF cells. However, significant differences were found in p24 antigen released by unstimulated and LPS stimulated cells. In contrast to HF cells, MDM cultures showed a significant inhibition of p24 antigen production when cells were stimulated with LPS prior to infection. HF cells were less susceptible to HIV-1 infection than MDM, and chemokines produced by HF cells did not result in further inhibition of HIV-1 infection. We found that in contrast to MDM, decreased susceptibility HF cells to HIV infection is not due to increased levels of chemokines, but to decreased HIV-1 coreceptor expression.