Secretory repertoire of HIV-infected human monocytes/macrophages

Abstract

Apart from lymphocytes, mononuclear phagocytes play an essential role as target cells for human immunodeficiency virus (HIV). Circulating blood monocytes (MOs) and tissue macrophages (M phi) may harbor and distribute the virus throughout the body. In addition, proinflammatory monokines [interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)] may contribute to the pathogenesis of HIV-mediated diseases. We have established a culture system on hydrophobic Teflon membranes for blood-borne MOs/M phi. Both freshly isolated MOs as well as MO-derived M phi could be infected with a monocytotropic HIV-1 isolate (HIV-1D117III) derived from a perinatally infected child. The virus production monitored by assay for viral antigen in cell-free supernatant is continuous for several weeks. We analyzed the stimulus response and the secretory repertoire of MOs/M phi early after infection with HIV as well as in long-term cultured, virus-replicating cells. Infected MOs/M phi respond to interferon-gamma more effectively than control cells as estimated from the release of neopterin. The response to lipopolysaccharide was regulated differently: whereas the proinflammatory cytokines IL-1, IL-6, IL-8 and TNF-alpha were up-regulated and even constitutively secreted upon infection, the production of the hematopoietin macrophage-colony-stimulating factor decreased. High levels of TNF-alpha and IL-1 might augment the infectibility of M phi by HIV in an autocrine manner. Our results may provide some explanation for the immunologic dysfunction, the hematopoietic failure and the chronic inflammatory disease occurring in HIV-infected patients.