Induction of cytokines by HIV-1 and its gp120 protein in human peripheral blood monocyte/macrophages and modulation of cytokine response during differentiation.
We previously reported that in vitro culture of human peripheral blood monocytes resulted in a time-dependent differentiation into macrophages and in an enhanced capacity for producing certain cytokines [i.e., tumor necrosis factor alpha, interleukin-6 (IL-6), and interferon-beta (IFN-beta)] in response to bacterial lipopolysaccharide (LPS). HIV-1 infection or gp120 treatment of monocyte/macrophages resulted in the induction of low levels of IFN-beta, which were very effective in restricting viral replication in 7-day cultured macrophages but not in freshly isolated cells. This enhanced response of macrophages was due to a higher sensitivity of these cells to the antiviral effect of IFN-beta. Consistent with this finding, 7-day cultured macrophages exhibited higher levels of type I IFN receptors than 1-day cultured monocytes. Treatment of monocyte/macrophages with gp120 also caused a marked increase in IL-10 secretion, regardless of the differentiation state. No IL-12 secretion was detected in monocyte/macrophage cultures treated with gp120 alone. However, consistent IL-12 secretion was found in 7-day cultured macrophages primed with IFN-beta and subsequently stimulated with gp120. Macrophages responded more efficiently than monocytes to the priming effect of IFN-beta for IL-12 production. This was consistent with a stronger antiviral response against vesicular stomatitis virus by these cells as well as with a higher expression of IFN-beta receptors. The finding that the acquisition of the macrophage phenotype is associated with an increased capacity to respond to environmental signals (such as type I and type II IFNs) underlines the importance of the differentiation process for the selection of a certain repertoire of responses that may allow these cells to have important functions in vivo.
Gessani
S
S
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Borghi
P
P
Fantuzzi
L
L
Varano
B
B
Conti
L
L
Puddu
P
P
Belardelli
F
F
D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D016899:Interferon-beta / Q000096:biosynthesis* / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000821:virology; D018448:Models, Immunological; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D017471:Receptors, Interferon / Q000096:biosynthesis*; D014779:Virus Replication / Q000276:immunology*
D016207:Cytokines; D015699:HIV Envelope Protein gp120; D008070:Lipopolysaccharides; D017471:Receptors, Interferon; D016753:Interleukin-10; D018664:Interleukin-12; D016899:Interferon-beta; D007371:Interferon-gamma