Human peripheral blood T cells, monocytes, and macrophages secrete macrophage inflammatory proteins 1α and 1β following stimulation with heat-inactivated Brucella abortus

Heat-killed Brucella abortus (HBa) has been proposed as a carrier for therapeutic vaccines for individuals with immunodeficiency, due to its abilities to induce interleukin-2 (IL-2) and gamma interferon (IFN-gamma) in both CD4(+) and CD8(+) T cells and to upregulate antigen-presenting cell functions (including IL-12 production). In the current study, we investigated the ability of HBa or lipopolysaccharide isolated from HBa (LPS-Ba) to elicit beta -chemokines, known to bind to the human immunodeficiency virus type 1 (HIV-1) coreceptor CCRS and to block viral cell entry. It was found that human peripheral blood mononuclear cells secreted beta -chemokines following stimulation with HBa, and this effect could not be blocked by anti-IFN-gamma neutralizing antibodies. Among purified T cells, macrophage inflammatory protein lo and Ip (MIP-1 alpha and MIP-1 beta, respectively) secretion was observed primarily in human CD8(+) T cells. The kinetics of beta -chemokine induction in T cells were slow (3 to 4 days). The majority of beta -chemokine-producing CD8(+) T cells also produced IFN-gamma following HBa stimulation, as determined by triple-color intracellular staining. A significant number of CD8(+) T cells contained stored MIP-1 beta that was released after HBa stimulation. Both HBa and LPS-Ba stimulated high levels of MIP-la and MIP-IP production in elutriated monocytes and even higher levels in macrophages. In these cells, beta -chemokine mRNA was upregulated within 30 min and proteins were secreted within 4 h of stimulation. The monocyte- and macrophage-derived beta -chemokines were sufficient to block CCR5-dependent HIV-1 envelope-mediated cell fusion. These data suggest that, in addition to the ability of HBa to elicit antigen-specific humoral and cellular immune responses, HBa-conjugated HIV-1 proteins or peptides would also generate innate chemokines with antiviral activity that could limit local viral spread during vaccination in vivo.