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C-C chemokines released by lipopolysaccharide (LPS)-stimulated human macrophages suppress HIV-1 infection in both macrophages and T cells.

Verani A, Scarlatti G, Comar M, Tresoldi E, Polo S, Giacca M, Lusso P, Siccardi AG, Vercelli D - J. Exp. Med. (1997)

Bottom Line: A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS.Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages.Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan, Italy.

ABSTRACT
Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C-C chemokines (RANTES, MIP-1 alpha, and MIP-1 beta) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

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Effects of neutralizing antibodies against HIV-1-inhibitory  cytokines. MDM were infected with HIV-1Ba-L and stimulated with LPS  (1 μg/ml), in presence or absence of neutralizing anti-IL-1Ra or anti-IL-10  antibodies (10 μg/ml). Culture supernatants were harvested daily, and  tested for p24 Ag secretion by ELISA. The data represent the mean of  two separate experiments. Control antibodies had no effect on p24 Ag secretion.
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Figure 5: Effects of neutralizing antibodies against HIV-1-inhibitory cytokines. MDM were infected with HIV-1Ba-L and stimulated with LPS (1 μg/ml), in presence or absence of neutralizing anti-IL-1Ra or anti-IL-10 antibodies (10 μg/ml). Culture supernatants were harvested daily, and tested for p24 Ag secretion by ELISA. The data represent the mean of two separate experiments. Control antibodies had no effect on p24 Ag secretion.

Mentions: Several monokines have been reported to suppress HIV-1 replication. Among them, IL-10 blocks HIV replication by inhibiting the secretion of endogenous TNF-α and IL-6 (28), cytokines that upregulate HIV expression. IL-1Ra, on the other hand, has been described to be produced by HIV-infected MDM in excess relative to IL-1α and IL-β, and thus effectively counteracts IL-1-mediated induction of HIV expression (29). We tested whether the release of these monokines was responsible for the LPS-induced inhibition of HIV-1 expression in MDM. To this purpose, neutralizing anti-IL-10 or antiIL-1Ra antibodies were added to MDM cultures infected with HIV-1 and stimulated with LPS. Fig. 5 shows that addition of neither antibody reversed the suppression of HIV-1 replication caused by LPS, thus ruling out a role of IL-10 and IL-1Ra in HIV-1 suppression.


C-C chemokines released by lipopolysaccharide (LPS)-stimulated human macrophages suppress HIV-1 infection in both macrophages and T cells.

Verani A, Scarlatti G, Comar M, Tresoldi E, Polo S, Giacca M, Lusso P, Siccardi AG, Vercelli D - J. Exp. Med. (1997)

Effects of neutralizing antibodies against HIV-1-inhibitory  cytokines. MDM were infected with HIV-1Ba-L and stimulated with LPS  (1 μg/ml), in presence or absence of neutralizing anti-IL-1Ra or anti-IL-10  antibodies (10 μg/ml). Culture supernatants were harvested daily, and  tested for p24 Ag secretion by ELISA. The data represent the mean of  two separate experiments. Control antibodies had no effect on p24 Ag secretion.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196157&req=5

Figure 5: Effects of neutralizing antibodies against HIV-1-inhibitory cytokines. MDM were infected with HIV-1Ba-L and stimulated with LPS (1 μg/ml), in presence or absence of neutralizing anti-IL-1Ra or anti-IL-10 antibodies (10 μg/ml). Culture supernatants were harvested daily, and tested for p24 Ag secretion by ELISA. The data represent the mean of two separate experiments. Control antibodies had no effect on p24 Ag secretion.
Mentions: Several monokines have been reported to suppress HIV-1 replication. Among them, IL-10 blocks HIV replication by inhibiting the secretion of endogenous TNF-α and IL-6 (28), cytokines that upregulate HIV expression. IL-1Ra, on the other hand, has been described to be produced by HIV-infected MDM in excess relative to IL-1α and IL-β, and thus effectively counteracts IL-1-mediated induction of HIV expression (29). We tested whether the release of these monokines was responsible for the LPS-induced inhibition of HIV-1 expression in MDM. To this purpose, neutralizing anti-IL-10 or antiIL-1Ra antibodies were added to MDM cultures infected with HIV-1 and stimulated with LPS. Fig. 5 shows that addition of neither antibody reversed the suppression of HIV-1 replication caused by LPS, thus ruling out a role of IL-10 and IL-1Ra in HIV-1 suppression.

Bottom Line: A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS.Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages.Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan, Italy.

ABSTRACT
Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C-C chemokines (RANTES, MIP-1 alpha, and MIP-1 beta) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

Show MeSH
Related in: MedlinePlus