Monocyte/macrophagederived CC chemokines and their modulation by HIV-1 and cytokines: a complex network of interactions influencing viral replication and AIDS

Abstract: Monocytes/macrophages are cells of the innate arm of the immune system and exert important regulatory effects on adaptive immune response. These cells also represent major targets of HIV infection and one of the main reservoirs. Notably, macrophage-tropic viruses are responsi-ble for the initial infection, predominate in the asymptomatic phase, and persist throughout infec-tion, even after the emergence of dual-tropic and T-tropic variants. Functional impairment of HIV-infected macrophages plays an important role in the immune dysregulation typical of AIDS. Recent studies have underlined the pivotal role of chemo-kines, cytokines, and their receptors in HIV patho-genesis. It is becoming increasingly apparent that the expression level of chemokine receptors, serv-ing as HIV coreceptors, influences the susceptibil-ity of a CD4 cell to viral infection and to certain HIV envelope-induced alterations in cellular func-tions. Numerous pathogens, including HIV, can stimulate the production of chemokines and cyto-kines, which in turn can modulate coreceptor availability, resulting in differential replication po-tential for R5 and X4 strains, depending on the microenvironment milieu. Thus, a complex net-work of interactions involving immune mediators produced by monocytes/macrophages and other cell types as a direct/indirect consequence of HIV infection is operative at all stages of the disease and may profoundly influence the extent of viral repli-cation, dissemination, and pathogenesis. J. Leukoc