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. 1998 Feb 2;187(3):439-44.
doi: 10.1084/jem.187.3.439.

Interleukin 10 increases CCR5 expression and HIV infection in human monocytes

S Sozzani  1 , S Ghezzi, G Iannolo, W Luini, A Borsatti, N Polentarutti, A Sica, M Locati, C Mackay, T N Wells, P Biswas, E Vicenzi, G Poli, A Mantovani
Affiliations

Interleukin 10 increases CCR5 expression and HIV infection in human monocytes

S Sozzani et al. J Exp Med. .

Abstract

The immunosuppressive and antiinflammatory cytokine interleukin (IL) 10 selectively upregulates the expression of the CC chemokine receptors CCR5, 2, and 1 in human monocytes by prolonging their mRNA half-life. IL-10-stimulated monocytes display an increased number of cell surface receptors for, and better chemotactic responsiveness to, relevant agonists than do control cells. In addition, IL-10-stimulated monocytes are more efficiently infected by HIV BaL. This effect was associated to the enhancement of viral entry through CCR5. These data add support to an emerging paradigm in which pro- and antiinflammatory molecules exert reciprocal and opposing influence on chemokine agonist production and receptor expression.

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Figures

Figure 1
Figure 1
Selective upregulation of CC chemokine receptors by IL-10. (A) Monocytes were stimulated with 10 ng/ml IL-10 for 4 h before Northern blot analysis. (B) Monocytes were stimulated with different concentrations of IL-10 for 4 h. (C) Monocytes were stimulated with 10 ng/ml IL-10 for different times. (D) Monocytes were incubated in the presence or absence of IL-10 (10 ng/ml) for 3 h and then Actinomycin-D (1 μg/ml; ActD; Sigma) was added for the indicated times. (E) Nuclear runoff analysis of CCR1, 2, and 5 genes. Human monocytes were incubated with 10 ng/ml IL-10 for different periods as indicated.
Figure 1
Figure 1
Selective upregulation of CC chemokine receptors by IL-10. (A) Monocytes were stimulated with 10 ng/ml IL-10 for 4 h before Northern blot analysis. (B) Monocytes were stimulated with different concentrations of IL-10 for 4 h. (C) Monocytes were stimulated with 10 ng/ml IL-10 for different times. (D) Monocytes were incubated in the presence or absence of IL-10 (10 ng/ml) for 3 h and then Actinomycin-D (1 μg/ml; ActD; Sigma) was added for the indicated times. (E) Nuclear runoff analysis of CCR1, 2, and 5 genes. Human monocytes were incubated with 10 ng/ml IL-10 for different periods as indicated.
Figure 1
Figure 1
Selective upregulation of CC chemokine receptors by IL-10. (A) Monocytes were stimulated with 10 ng/ml IL-10 for 4 h before Northern blot analysis. (B) Monocytes were stimulated with different concentrations of IL-10 for 4 h. (C) Monocytes were stimulated with 10 ng/ml IL-10 for different times. (D) Monocytes were incubated in the presence or absence of IL-10 (10 ng/ml) for 3 h and then Actinomycin-D (1 μg/ml; ActD; Sigma) was added for the indicated times. (E) Nuclear runoff analysis of CCR1, 2, and 5 genes. Human monocytes were incubated with 10 ng/ml IL-10 for different periods as indicated.
Figure 1
Figure 1
Selective upregulation of CC chemokine receptors by IL-10. (A) Monocytes were stimulated with 10 ng/ml IL-10 for 4 h before Northern blot analysis. (B) Monocytes were stimulated with different concentrations of IL-10 for 4 h. (C) Monocytes were stimulated with 10 ng/ml IL-10 for different times. (D) Monocytes were incubated in the presence or absence of IL-10 (10 ng/ml) for 3 h and then Actinomycin-D (1 μg/ml; ActD; Sigma) was added for the indicated times. (E) Nuclear runoff analysis of CCR1, 2, and 5 genes. Human monocytes were incubated with 10 ng/ml IL-10 for different periods as indicated.
Figure 1
Figure 1
Selective upregulation of CC chemokine receptors by IL-10. (A) Monocytes were stimulated with 10 ng/ml IL-10 for 4 h before Northern blot analysis. (B) Monocytes were stimulated with different concentrations of IL-10 for 4 h. (C) Monocytes were stimulated with 10 ng/ml IL-10 for different times. (D) Monocytes were incubated in the presence or absence of IL-10 (10 ng/ml) for 3 h and then Actinomycin-D (1 μg/ml; ActD; Sigma) was added for the indicated times. (E) Nuclear runoff analysis of CCR1, 2, and 5 genes. Human monocytes were incubated with 10 ng/ml IL-10 for different periods as indicated.
Figure 2
Figure 2
Augmented expression of functional CC chemokine receptors and upregulation of HIV infection by IL-10. (A) Effect on chemotaxis. Monocytes were cultured for 16 h with medium or IL-10 (10 ng/ ml) and tested for chemotaxis to a suboptimal concentration of MCP-1 (1 ng/ml) or MIP-1β (10 ng/ml). Values are mean (± SE, three replicates) number of migrated cells after subtraction of spontaneous migration that was not affected by IL-10 (data not shown). (B) Surface expression of CCR5. Monocytes were exposed to IL-10 (10 ng/ml) for 16 h and surface expression was determined by flow cytometry using the 5C7-18 anti-CCR5 mAb. Dots, irrelevant mAb; broken line, control monocytes stained with anti-CCR5; continuous line, IL-10–treated monocytes stained with anti-CCR5. (C) Kinetics of CCR5 expression in control and HIV-infected monocytes cultured for the time indicated with 10 ng/ml IL-10. Results from a single donor representative of two to four tested are expressed as relative fluorescence index as described in Materials and Methods. (D) Effect of IL-10 on HIV infection of monocytes. Cells were incubated in 48-well tissue culture plastic plates in the presence or absence of IL-10 (0.1 ng/ml) for 6 h before incubation for 30 min with RANTES (200 ng/ml) and infection with the macrophage-tropic BaL strain of HIV-1. Mg2+-dependent reverse transcriptase activity was measured in the culture supernatants (24).
Figure 3
Figure 3
Kinetics of proviral HIV DNA accumulation. Monocytes were stimulated with IL-10 (10 ng/ml) for 6 h in the presence and absence of 200 ng/ml of AOP-RANTES for 30 min before infection with HIV-1 Bal. Aliquots were harvested 1, 16, and 40 h after infection and tested for proviral DNA synthesis.
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